Chaperone (protein)

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A top-view of the GroES/GroEL bacterial chaperone complex model GroES-GroEL top.png
A top-view of the GroES/GroEL bacterial chaperone complex model

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to assist large proteins in proper protein folding during or after synthesis, and after partial denaturation. Chaperones are also involved in the translocation of proteins for proteolysis.

Contents

The first molecular chaperones discovered were a type of assembly chaperones which assist in the assembly of nucleosomes from folded histones and DNA. [1] [2] One major function of molecular chaperones is to prevent the aggregation of misfolded proteins, thus many chaperone proteins are classified as heat shock proteins, as the tendency for protein aggregation is increased by heat stress.

The majority of molecular chaperones do not convey any steric information for protein folding, and instead assist in protein folding by binding to and stabilizing folding intermediates until the polypeptide chain is fully translated. The specific mode of function of chaperones differs based on their target proteins and location. Various approaches have been applied to study the structure, dynamics and functioning of chaperones. Bulk biochemical measurements have informed us on the protein folding efficiency, and prevention of aggregation when chaperones are present during protein folding. Recent advances in single-molecule analysis [3] have brought insights into structural heterogeneity of chaperones, folding intermediates and affinity of chaperones for unstructured and structured protein chains.

Functions of molecular chaperones

Many chaperones are heat shock proteins, that is, proteins expressed in response to elevated temperatures or other cellular stresses. [4] Heat shock protein chaperones are classified based on their observed molecular weights into Hsp60, Hsp70, Hsp90, Hsp104, and small Hsps. [5] The Hsp60 family of protein chaperones are termed chaperonins, and are characterized by a stacked double-ring structure and are found in prokaryotes, in the cytosol of eukaryotes, and in mitochondria.

Some chaperone systems work as foldases: they support the folding of proteins in an ATP-dependent manner (for example, the GroEL/GroES or the DnaK/DnaJ/GrpE system). Although most newly synthesized proteins can fold in absence of chaperones, a minority strictly requires them for the same. Other chaperones work as holdases: they bind folding intermediates to prevent their aggregation, for example DnaJ or Hsp33. [6] Chaperones can also work as disaggregases, which interact with aberrant protein assemblies and revert them to monomers. [7] Some chaperones can assist in protein degradation, leading proteins to protease systems, such as the ubiquitin-proteasome system in eukaryotes. [8] Chaperone proteins participate in the folding of over half of all mammalian proteins.[ citation needed ]

Macromolecular crowding may be important in chaperone function. The crowded environment of the cytosol can accelerate the folding process, since a compact folded protein will occupy less volume than an unfolded protein chain. [9] However, crowding can reduce the yield of correctly folded protein by increasing protein aggregation. [10] [11] Crowding may also increase the effectiveness of the chaperone proteins such as GroEL, [12] which could counteract this reduction in folding efficiency. [13] Some highly specific 'steric chaperones' convey unique structural information onto proteins, which cannot be folded spontaneously. Such proteins violate Anfinsen's dogma, [14] requiring protein dynamics to fold correctly.

Other types of chaperones are involved in transport across membranes, for example membranes of the mitochondria and endoplasmic reticulum (ER) in eukaryotes. A bacterial translocation-specific chaperone SecB maintains newly synthesized precursor polypeptide chains in a translocation-competent (generally unfolded) state and guides them to the translocon. [15]

New functions for chaperones continue to be discovered, such as bacterial adhesin activity, induction of aggregation towards non-amyloid aggregates, [16] suppression of toxic protein oligomers via their clustering, [17] [18] and in responding to diseases linked to protein aggregation [19] and cancer maintenance. [20]

Human chaperone proteins

In human cell lines, chaperone proteins were found to compose ~10% of the gross proteome mass, [21] and are ubiquitously and highly expressed across human tissues.

Chaperones are found extensively in the endoplasmic reticulum (ER), since protein synthesis often occurs in this area.

Endoplasmic reticulum

In the endoplasmic reticulum (ER) there are general, lectin- and non-classical molecular chaperones that moderate protein folding.

Nomenclature and examples of chaperone families

There are many different families of chaperones; each family acts to aid protein folding in a different way. In bacteria like E. coli , many of these proteins are highly expressed under conditions of high stress, for example, when the bacterium is placed in high temperatures, thus heat shock protein chaperones are the most extensive.

A variety of nomenclatures are in use for chaperones. As heat shock proteins, the names are classically formed by "Hsp" followed by the approximate molecular mass in kilodaltons; such names are commonly used for eukaryotes such as yeast. The bacterial names have more varied forms, and refer directly to their apparent function at discovery. For example, "GroEL" originally stands for "phage growth defect, overcome by mutation in phage gene E, large subunit". [25]

Hsp10 and Hsp60

Hsp10/60 (GroEL/GroES complex in E. coli) is the best characterized large (~ 1 MDa) chaperone complex. GroEL (Hsp60) is a double-ring 14mer with a hydrophobic patch at its opening; it is so large it can accommodate native folding of 54-kDa GFP in its lumen. GroES (Hsp10) is a single-ring heptamer that binds to GroEL in the presence of ATP or ADP. GroEL/GroES may not be able to undo previous aggregation, but it does compete in the pathway of misfolding and aggregation. [26] Also acts in mitochondrial matrix as molecular chaperone.

Hsp70 and Hsp40

hsp70 pocket for substrate binding Hsp70pocket.png
hsp70 pocket for substrate binding

Hsp70 (DnaK in E. coli) is perhaps the best characterized small (~ 70 kDa) chaperone. The Hsp70 proteins are aided by Hsp40 proteins (DnaJ in E. coli), which increase the ATP consumption rate and activity of the Hsp70s. The two protein are named "Dna" in bacteria because they were initially identified as being required for E. coli DNA replication. [27]

It has been noted that increased expression of Hsp70 proteins in the cell results in a decreased tendency toward apoptosis. Although a precise mechanistic understanding has yet to be determined, it is known that Hsp70s have a high-affinity bound state to unfolded proteins when bound to ADP, and a low-affinity state when bound to ATP.

It is thought that many Hsp70s crowd around an unfolded substrate, stabilizing it and preventing aggregation until the unfolded molecule folds properly, at which time the Hsp70s lose affinity for the molecule and diffuse away. [28] Hsp70 also acts as a mitochondrial and chloroplastic molecular chaperone in eukaryotes.

Hsp90

Hsp90 (HtpG in E. coli [lower-alpha 1] ) may be the least understood chaperone. Its molecular weight is about 90 kDa, and it is necessary for viability in eukaryotes (possibly for prokaryotes as well). Heat shock protein 90 (Hsp90) is a molecular chaperone essential for activating many signaling proteins in the eukaryotic cell.

Each Hsp90 has an ATP-binding domain, a middle domain, and a dimerization domain. Originally thought to clamp onto their substrate protein (also known as a client protein) upon binding ATP, the recently published structures by Vaughan et al. and Ali et al. indicate that client proteins may bind externally to both the N-terminal and middle domains of Hsp90. [29] [30]

Hsp90 may also require co-chaperones-like immunophilins, Sti1, p50 (Cdc37), and Aha1, and also cooperates with the Hsp70 chaperone system. [31] [32]

Hsp100

Hsp100 (Clp family in E. coli) proteins have been studied in vivo and in vitro for their ability to target and unfold tagged and misfolded proteins.

Proteins in the Hsp100/Clp family form large hexameric structures with unfoldase activity in the presence of ATP. These proteins are thought to function as chaperones by processively threading client proteins through a small 20 Å (2 nm) pore, thereby giving each client protein a second chance to fold.

Some of these Hsp100 chaperones, like ClpA and ClpX, associate with the double-ringed tetradecameric serine protease ClpP; instead of catalyzing the refolding of client proteins, these complexes are responsible for the targeted destruction of tagged and misfolded proteins.

Hsp104, the Hsp100 of Saccharomyces cerevisiae, is essential for the propagation of many yeast prions. Deletion of the HSP104 gene results in cells that are unable to propagate certain prions.

Bacteriophage

The genes of bacteriophage (phage) T4 that encode proteins with a role in determining phage T4 structure were identified using conditional lethal mutants. [33] Most of these proteins proved to be either major or minor structural components of the completed phage particle. However among the gene products (gps) necessary for phage assembly, Snustad [34] identified a group of gps that act catalytically rather than being incorporated themselves into the phage structure. These gps were gp26, gp31, gp38, gp51, gp28, and gp4 [gene 4 is synonymous with genes 50 and 65, and thus the gp can be designated gp4(50)(65)]. The first four of these six gene products have since been recognized as being chaperone proteins. Additionally, gp40, gp57A, gp63 and gpwac have also now been identified as chaperones.

Phage T4 morphogenesis is divided into three independent pathways: the head, the tail and the long tail fiber pathways as detailed by Yap and Rossman. [35] With regard to head morphogenesis, chaperone gp31 interacts with the bacterial host chaperone GroEL to promote proper folding of the major head capsid protein gp23. [36] [35] Chaperone gp40 participates in the assembly of gp20, thus aiding in the formation of the connector complex that initiates head procapsid assembly. [36] [35] Gp4(50)(65), although not specifically listed as a chaperone, acts catalytically as a nuclease that appears to be essential for morphogenesis by cleaving packaged DNA to enable the joining of heads to tails. [37]

During overall tail assembly, chaperone proteins gp26 and gp51 are necessary for baseplate hub assembly. [38] Gp57A is required for correct folding of gp12, a structural component of the baseplate short tail fibers. [38]

Synthesis of the long tail fibers depends on the chaperone protein gp57A that is needed for the trimerization of gp34 and gp37, the major structural proteins of the tail fibers. [36] [35] The chaperone protein gp38 is also required for the proper folding of gp37. [38] [39] Chaperone proteins gp63 and gpwac are employed in attachment of the long tail fibers to the tail baseplate. [38]

History

The investigation of chaperones has a long history. [40] The term "molecular chaperone" appeared first in the literature in 1978, and was invented by Ron Laskey to describe the ability of a nuclear protein called nucleoplasmin to prevent the aggregation of folded histone proteins with DNA during the assembly of nucleosomes. [41] The term was later extended by R. John Ellis in 1987 to describe proteins that mediated the post-translational assembly of protein complexes. [42] In 1988, it was realised that similar proteins mediated this process in both prokaryotes and eukaryotes. [43] The details of this process were determined in 1989, when the ATP-dependent protein folding was demonstrated in vitro. [44]

Clinical significance

There are many disorders associated with mutations in genes encoding chaperones (i.e. multisystem proteinopathy) that can affect muscle, bone and/or the central nervous system. [45]

See also

Commons-logo.svg Media related to Chaperone proteins at Wikimedia Commons

Notes

  1. ↑ Initially identified as Drosophilia Hsp83 homologue. Name stands for "high temperature protein G".

Related Research Articles

<span class="mw-page-title-main">Lambda phage</span> Bacteriophage that infects Escherichia coli

Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

<span class="mw-page-title-main">Hsp70</span> Family of heat shock proteins

The 70 kilodalton heat shock proteins are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an important part of the cell's machinery for protein folding, performing chaperoning functions, and helping to protect cells from the adverse effects of physiological stresses. Additionally, membrane-bound Hsp70s have been identified as a potential target for cancer therapies and their extracellularly localized counterparts have been identified as having both membrane-bound and membrane-free structures.

<span class="mw-page-title-main">Hsp90</span> Heat shock proteins with a molecular mass around 90kDa

Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.

<i>Escherichia virus T4</i> Species of bacteriophage

Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a double-stranded DNA virus in the subfamily Tevenvirinae from the family Myoviridae. T4 is capable of undergoing only a lytic life cycle and not the lysogenic life cycle. The species was formerly named T-even bacteriophage, a name which also encompasses, among other strains, Enterobacteria phage T2, Enterobacteria phage T4 and Enterobacteria phage T6.

<span class="mw-page-title-main">GroEL</span> Protein-coding gene in the species Homo sapiens

GroEL is a protein which belongs to the chaperonin family of molecular chaperones, and is found in many bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES. In eukaryotes the organellar proteins Hsp60 and Hsp10 are structurally and functionally nearly identical to GroEL and GroES, respectively, due to their endosymbiotic origin.

<span class="mw-page-title-main">GroES</span> Protein-coding gene in the species Homo sapiens

Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the HSPE1 gene. The homolog in E. coli is GroES that is a chaperonin which usually works in conjunction with GroEL.

<span class="mw-page-title-main">Chaperonin</span> InterPro Family

HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 belong to a large class of molecules that assist protein folding, called molecular chaperones.

<span class="mw-page-title-main">Heat shock response</span> Type of cellular stress response

The heat shock response (HSR) is a cell stress response that increases the number of molecular chaperones to combat the negative effects on proteins caused by stressors such as increased temperatures, oxidative stress, and heavy metals. In a normal cell, proteostasis must be maintained because proteins are the main functional units of the cell. Many proteins take on a defined configuration in a process known as protein folding in order to perform their biological functions. If these structures are altered, critical processes could be affected, leading to cell damage or death. The heat shock response can be employed under stress to induce the expression of heat shock proteins (HSP), many of which are molecular chaperones, that help prevent or reverse protein misfolding and provide an environment for proper folding.

<span class="mw-page-title-main">T7 phage</span> Species of virus

Bacteriophage T7 is a bacteriophage, a virus that infects bacteria. It infects most strains of Escherichia coli and relies on these hosts to propagate. Bacteriophage T7 has a lytic life cycle, meaning that it destroys the cell it infects. It also possesses several properties that make it an ideal phage for experimentation: its purification and concentration have produced consistent values in chemical analyses; it can be rendered noninfectious by exposure to UV light; and it can be used in phage display to clone RNA binding proteins.

Salmonella virus P22 is a bacteriophage in the Podoviridae family that infects Salmonella typhimurium. Like many phages, it has been used in molecular biology to induce mutations in cultured bacteria and to introduce foreign genetic material. P22 has been used in generalized transduction and is an important tool for investigating Salmonella genetics.

Co-chaperones are proteins that assist chaperones in protein folding and other functions. Co-chaperones are the non-client binding molecules that assist in protein folding mediated by Hsp70 and Hsp90. They are particularly essential in stimulation of the ATPase activity of these chaperone proteins. There are a great number of different co-chaperones however based on their domain structure most of them fall into two groups: J-domain proteins and tetratricopeptide repeats (TPR).

<span class="mw-page-title-main">HSP90AB1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.

<span class="mw-page-title-main">Binding immunoglobulin protein</span> Protein-coding gene in the species Homo sapiens

Binding immunoglobulin protein (BiPS) also known as 78 kDa glucose-regulated protein (GRP-78) or heat shock 70 kDa protein 5 (HSPA5) is a protein that in humans is encoded by the HSPA5 gene.

<span class="mw-page-title-main">HSPA1L</span> Protein-coding gene in the species Homo sapiens

Heat shock 70 kDa protein 1L is a protein that in humans is encoded by the HSPA1L gene on chromosome 6. As a member of the heat shock protein 70 (Hsp70) family and a chaperone protein, it facilitates the proper folding of newly translated and misfolded proteins, as well as stabilize or degrade mutant proteins. Its functions contribute to biological processes including signal transduction, apoptosis, protein homeostasis, and cell growth and differentiation. It has been associated with an extensive number of cancers, neurodegenerative diseases, cell senescence and aging, and Graft-versus-host disease.

<span class="mw-page-title-main">Protein aggregation</span> Accumulation of clumps of misfolded or disordered proteins

In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate either intra- or extracellularly. Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease.

Proteostasis is the dynamic regulation of a balanced, functional proteome. The proteostasis network includes competing and integrated biological pathways within cells that control the biogenesis, folding, trafficking, and degradation of proteins present within and outside the cell. Loss of proteostasis is central to understanding the cause of diseases associated with excessive protein misfolding and degradation leading to loss-of-function phenotypes, as well as aggregation-associated degenerative disorders. Therapeutic restoration of proteostasis may treat or resolve these pathologies. Cellular proteostasis is key to ensuring successful development, healthy aging, resistance to environmental stresses, and to minimize homeostatic perturbations from pathogens such as viruses. Cellular mechanisms for maintaining proteostasis include regulated protein translation, chaperone assisted protein folding, and protein degradation pathways. Adjusting each of these mechanisms based on the need for specific proteins is essential to maintain all cellular functions relying on a correctly folded proteome.

<span class="mw-page-title-main">Chaperone DnaJ</span>

In molecular biology, chaperone DnaJ, also known as Hsp40, is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.

Chaperones, also called molecular chaperones, are proteins that assist other proteins in assuming their three-dimensional fold, which is necessary for protein function. However, the fold of a protein is sensitive to environmental conditions, such as temperature and pH, and thus chaperones are needed to keep proteins in their functional fold across various environmental conditions. Chaperones are an integral part of a cell's protein quality control network by assisting in protein folding and are ubiquitous across diverse biological taxa. Since protein folding, and therefore protein function, is susceptible to environmental conditions, chaperones could represent an important cellular aspect of biodiversity and environmental tolerance by organisms living in hazardous conditions. Chaperones also affect the evolution of proteins in general, as many proteins fundamentally require chaperones to fold or are naturally prone to misfolding, and therefore mitigates protein aggregation.

<span class="mw-page-title-main">Sue Wickner</span> American biochemist and geneticist

Sue Hengren Wickner is an American biochemist and geneticist who is a distinguished investigator and the head of the DNA Molecular Biology section of the National Institutes of Health. Her laboratory is under the National Cancer Institute and is located in the Center for Cancer Research (NCI/CCR).

<span class="mw-page-title-main">GrpE</span> InterPro Family

GrpE is a bacterial nucleotide exchange factor that is important for regulation of protein folding machinery, as well as the heat shock response. It is a heat-inducible protein and during stress it prevents unfolded proteins from accumulating in the cytoplasm. Accumulation of unfolded proteins in the cytoplasm can lead to cell death.

References

  1. ↑ Richardson RT, Alekseev OM, Grossman G, Widgren EE, Thresher R, Wagner EJ, et al. (July 2006). "Nuclear autoantigenic sperm protein (NASP), a linker histone chaperone that is required for cell proliferation". The Journal of Biological Chemistry. 281 (30): 21526–34. doi: 10.1074/jbc.M603816200 . PMID   16728391.
  2. ↑ Alekseev OM, Richardson RT, Alekseev O, O'Rand MG (May 2009). "Analysis of gene expression profiles in HeLa cells in response to overexpression or siRNA-mediated depletion of NASP". Reproductive Biology and Endocrinology. 7: 45. doi:10.1186/1477-7827-7-45. PMC   2686705 . PMID   19439102.
  3. ↑ [Chaperone Action at the Single-Molecule Level http://pubs.acs.org/doi/abs/10.1021/cr400326k]
  4. ↑ Ellis RJ, van der Vies SM (1991). "Molecular chaperones". Annual Review of Biochemistry. 60: 321–347. doi:10.1146/annurev.bi.60.070191.001541. PMID   1679318.
  5. ↑ Bascos NA, Landry SJ (December 2019). "A History of Molecular Chaperone Structures in the Protein Data Bank". International Journal of Molecular Sciences. 20 (24): 6195. doi: 10.3390/ijms20246195 . PMC   6940948 . PMID   31817979.
  6. ↑ Hoffmann JH, Linke K, Graf PC, Lilie H, Jakob U (January 2004). "Identification of a redox-regulated chaperone network". The EMBO Journal. 23 (1): 160–8. doi:10.1038/sj.emboj.7600016. PMC   1271656 . PMID   14685279.
  7. ↑ Nillegoda NB, Kirstein J, Szlachcic A, Berynskyy M, Stank A, Stengel F, et al. (August 2015). "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation". Nature. 524 (7564): 247–51. Bibcode:2015Natur.524..247N. doi:10.1038/nature14884. PMC   4830470 . PMID   26245380.
  8. ↑ Balchin D, Hayer-Hartl M, Hartl FU (July 2016). "In vivo aspects of protein folding and quality control". Science. 353 (6294): aac4354. doi:10.1126/science.aac4354. hdl: 11858/00-001M-0000-002B-0856-C . PMID   27365453. S2CID   5174431.
  9. ↑ van den Berg B, Wain R, Dobson CM, Ellis RJ (August 2000). "Macromolecular crowding perturbs protein refolding kinetics: implications for folding inside the cell". The EMBO Journal. 19 (15): 3870–5. doi:10.1093/emboj/19.15.3870. PMC   306593 . PMID   10921869.
  10. ↑ van den Berg B, Ellis RJ, Dobson CM (December 1999). "Effects of macromolecular crowding on protein folding and aggregation". The EMBO Journal. 18 (24): 6927–33. doi:10.1093/emboj/18.24.6927. PMC   1171756 . PMID   10601015.
  11. ↑ Ellis RJ, Minton AP (May 2006). "Protein aggregation in crowded environments". Biological Chemistry. 387 (5): 485–97. doi:10.1515/BC.2006.064. PMID   16740119. S2CID   7336464.
  12. ↑ Martin J, Hartl FU (February 1997). "The effect of macromolecular crowding on chaperonin-mediated protein folding". Proceedings of the National Academy of Sciences of the United States of America. 94 (4): 1107–12. Bibcode:1997PNAS...94.1107M. doi: 10.1073/pnas.94.4.1107 . PMC   19752 . PMID   9037014.
  13. ↑ Ellis RJ (2007). Protein misassembly: macromolecular crowding and molecular chaperones . pp.  1–13. doi:10.1007/978-0-387-39975-1_1. ISBN   978-0-387-39974-4. PMID   17205670.{{cite book}}: |journal= ignored (help)
  14. ↑ Pauwels K, Van Molle I, Tommassen J, Van Gelder P (May 2007). "Chaperoning Anfinsen: the steric foldases" (PDF). Molecular Microbiology. 64 (4): 917–22. doi:10.1111/j.1365-2958.2007.05718.x. PMID   17501917. S2CID   6435829. Archived from the original (PDF) on 2012-05-23.
  15. ↑ Zhou J, Xu Z (October 2005). "The structural view of bacterial translocation-specific chaperone SecB: implications for function" (PDF). Molecular Microbiology. 58 (2): 349–57. doi:10.1111/j.1365-2958.2005.04842.x. hdl: 2027.42/74325 . PMID   16194224. S2CID   33227532.
  16. ↑ Specht S, Miller SB, Mogk A, Bukau B (14 November 2011). "Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae". J. Cell Biol. 195 (4): 617–29. doi:10.1083/jcb.201106037. PMC   3257523 . PMID   22065637.
  17. ↑ Ojha J, Masilamoni G, Dunlap D, Udoff RA, Cashikar AG (August 2011). "Sequestration of toxic oligomers by HspB1 as a cytoprotective mechanism". Mol. Cell. Biol. 31 (15): 3146–57. doi:10.1128/MCB.01187-10. PMC   3147607 . PMID   21670152.
  18. ↑ Mannini B, Cascella R, Zampagni M, van Waarde-Verhagen M, Meehan S, Roodveldt C, Campioni S, Boninsegna M, Penco A, Relini A, Kampinga HH, Dobson CM, Wilson MR, Cecchi C, Chiti F (31 July 2012). "Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers". Proc. Natl. Acad. Sci. USA. 109 (31): 12479–84. Bibcode:2012PNAS..10912479M. doi: 10.1073/pnas.1117799109 . PMC   3411936 . PMID   22802614.
  19. ↑ Sadigh-Eteghad S, Majdi A, Talebi M, Mahmoudi J, Babri S (May 2015). "Regulation of nicotinic acetylcholine receptors in Alzheimer׳s disease: a possible role of chaperones". European Journal of Pharmacology. 755: 34–41. doi:10.1016/j.ejphar.2015.02.047. PMID   25771456. S2CID   31929001.
  20. ↑ Salamanca HH, Antonyak MA, Cerione RA, Shi H, Lis JT (2014). "Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer". PLOS ONE. 9 (5): e96330. Bibcode:2014PLoSO...996330S. doi: 10.1371/journal.pone.0096330 . PMC   4011729 . PMID   24800749.
  21. ↑ Finka A, Goloubinoff P (September 2013). "Proteomic data from human cell cultures refine mechanisms of chaperone-mediated protein homeostasis". Cell Stress & Chaperones. 18 (5): 591–605. doi:10.1007/s12192-013-0413-3. PMC   3745260 . PMID   23430704.
  22. ↑ Ruoppolo M, Orrù S, Talamo F, Ljung J, Pirneskoski A, Kivirikko KI, et al. (May 2003). "Mutations in domain a' of protein disulfide isomerase affect the folding pathway of bovine pancreatic ribonuclease A". Protein Science. 12 (5): 939–52. doi:10.1110/ps.0242803. PMC   2323865 . PMID   12717017.
  23. ↑ Soluble complexes of target proteins and peptidyl prolyl isomerase ...
  24. ↑ Frickel EM, Riek R, Jelesarov I, Helenius A, Wuthrich K, Ellgaard L (February 2002). "TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain". Proceedings of the National Academy of Sciences of the United States of America. 99 (4): 1954–9. Bibcode:2002PNAS...99.1954F. doi: 10.1073/pnas.042699099 . PMC   122301 . PMID   11842220.
  25. ↑ Smith, Tracy (1 December 1999). "The discovery of chaperonins". Nature Structural Biology. 6 (12): 1090. doi: 10.1038/70015 . PMID   10581544. S2CID   6158370.
  26. ↑ Fenton WA, Horwich AL (May 2003). "Chaperonin-mediated protein folding: fate of substrate polypeptide". Quarterly Reviews of Biophysics. 36 (2): 229–56. doi:10.1017/S0033583503003883. PMID   14686103. S2CID   10328521.
  27. ↑ Yochem, J; Uchida, H; Sunshine, M; Saito, H; Georgopoulos, CP; Feiss, M (4 August 1978). "Genetic analysis of two genes, dnaJ and dnaK, necessary for Escherichia coli and bacteriophage lambda DNA replication". Molecular & General Genetics. 164 (1): 9–14. doi:10.1007/BF00267593. PMID   360041. S2CID   28144214.
  28. ↑ Mayer MP, Bukau B (March 2005). "Hsp70 chaperones: cellular functions and molecular mechanism". Cellular and Molecular Life Sciences. 62 (6): 670–84. doi:10.1007/s00018-004-4464-6. PMC   2773841 . PMID   15770419.
  29. ↑ Vaughan CK, Gohlke U, Sobott F, Good VM, Ali MM, Prodromou C, et al. (September 2006). "Structure of an Hsp90-Cdc37-Cdk4 complex". Molecular Cell. 23 (5): 697–707. doi:10.1016/j.molcel.2006.07.016. PMC   5704897 . PMID   16949366.
  30. ↑ Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, et al. (April 2006). "Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex". Nature. 440 (7087): 1013–7. Bibcode:2006Natur.440.1013A. doi:10.1038/nature04716. PMC   5703407 . PMID   16625188.
  31. ↑ Terasawa K, Minami M, Minami Y (April 2005). "Constantly updated knowledge of Hsp90". Journal of Biochemistry. 137 (4): 443–7. doi: 10.1093/jb/mvi056 . PMID   15858167.
  32. ↑ Pearl LH, Prodromou C (2006). "Structure and mechanism of the Hsp90 molecular chaperone machinery". Annual Review of Biochemistry. 75: 271–94. doi:10.1146/annurev.biochem.75.103004.142738. PMID   16756493.
  33. ↑ Edgar RS, Epstein RH. The genetics of a bacterial virus. Sci Am. 1965;212:70-78. doi:10.1038/scientificamerican0265-70
  34. ↑ Snustad DP. Dominance interactions in Escherichia coli cells mixedly infected with bacteriophage T4D wild-type and amber mutants and their possible implications as to type of gene-product function: catalytic vs. stoichiometric. Virology. 1968;35(4):550-563. doi:10.1016/0042-6822(68)90285-7
  35. 1 2 3 4 Yap ML, Rossmann MG. Structure and function of bacteriophage T4. Future Microbiol. 2014;9(12):1319-1327. doi:10.2217/fmb.14.91
  36. 1 2 3 Marusich EI, Kurochkina LP, Mesyanzhinov VV. Chaperones in bacteriophage T4 assembly. Biochemistry (Mosc). 1998;63(4):399-406
  37. ↑ Benler S, Hung SH, Vander Griend JA, Peters GA, Rohwer F, Segall AM. Gp4 is a nuclease required for morphogenesis of T4-like bacteriophages. Virology. 2020;543:7-12. doi:10.1016/j.virol.2020.01.008
  38. 1 2 3 4 Leiman PG, Arisaka F, van Raaij MJ, et al. Morphogenesis of the T4 tail and tail fibers. Virol J. 2010;7:355. Published 2010 Dec 3. doi:10.1186/1743-422X-7-355
  39. ↑ Hyman P, van Raaij M. Bacteriophage T4 long tail fiber domains. Biophys Rev. 2018;10(2):463-471. doi:10.1007/s12551-017-0348-5
  40. ↑ Ellis RJ (September 1996). "Discovery of molecular chaperones". Cell Stress & Chaperones. 1 (3): 155–60. PMC   248474 . PMID   9222600.
  41. ↑ Laskey RA, Honda BM, Mills AD, Finch JT (October 1978). "Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA". Nature. 275 (5679): 416–20. Bibcode:1978Natur.275..416L. doi:10.1038/275416a0. PMID   692721. S2CID   2535641.
  42. ↑ Ellis J (1987). "Proteins as molecular chaperones". Nature. 328 (6129): 378–9. Bibcode:1987Natur.328..378E. doi:10.1038/328378a0. PMID   3112578. S2CID   4337273.
  43. ↑ Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, et al. (May 1988). "Homologous plant and bacterial proteins chaperone oligomeric protein assembly". Nature. 333 (6171): 330–4. Bibcode:1988Natur.333..330H. doi:10.1038/333330a0. PMID   2897629. S2CID   4325057.
  44. ↑ Goloubinoff P, Christeller JT, Gatenby AA, Lorimer GH (1989). "Reconstitution of active dimeric ribulose bisphosphate carboxylase from an unfoleded state depends on two chaperonin proteins and Mg-ATP". Nature. 342 (6252): 884–9. Bibcode:1989Natur.342..884G. doi:10.1038/342884a0. PMID   10532860. S2CID   4319510.
  45. ↑ Taylor JP (August 2015). "Multisystem proteinopathy: intersecting genetics in muscle, bone, and brain degeneration". Neurology. 85 (8): 658–60. doi:10.1212/WNL.0000000000001862. PMID   26208960. S2CID   42203997.
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