Peptide microarray

Last updated
Peptide microarray
Other namesPeptide chip, peptide array
UsesTo study binding properties, specificity and functionality and kinetics of protein-peptide or protein-protein interactions

A peptide microarray (also commonly known as peptide chip or peptide epitope microarray) is a collection of peptides displayed on a solid surface, usually a glass or plastic chip. Peptide chips are used by scientists in biology, medicine and pharmacology to study binding properties and functionality and kinetics of protein-protein interactions in general. In basic research, peptide microarrays are often used to profile an enzyme (like kinase, phosphatase, protease, acetyltransferase, histone deacetylase etc.), to map an antibody epitope or to find key residues for protein binding. Practical applications are seromarker discovery, profiling of changing humoral immune responses of individual patients during disease progression, monitoring of therapeutic interventions, patient stratification and development of diagnostic tools and vaccines.

Contents

An example of a peptide array used for epitope identification and specificity mapping. Journal.pone.0068902.g001.png
An example of a peptide array used for epitope identification and specificity mapping.

Principle

The assay principle of peptide microarrays is similar to an ELISA protocol. The peptides (up to tens of thousands in several copies) are linked to the surface of a glass chip typically the size and shape of a microscope slide. This peptide chip can directly be incubated with a variety of different biological samples like purified enzymes or antibodies, patient or animal sera, cell lysates and then be detected through a label-dependent fashion, for example, by a primary antibody that targets the bound protein or modified substrates. After several washing steps a secondary antibody with the needed specificity (e.g. anti IgG human/mouse or anti phosphotyrosine or anti myc) is applied. Usually, the secondary antibody is tagged by a fluorescence label that can be detected by a fluorescence scanner. [2] Other label-dependent detection methods includes chemiluminescence, colorimetric or autoradiography.

Label-dependent assays are rapid and convenient to perform, but risk giving rise to false positive and negative results. [3] More recently, label-free detection including surface plasmon resonance (SPR) spectroscopy, mass spectrometry (MS) and many other optical biosensors [4] [5] [6] [7] have been employed to measuring a broad range of enzyme activities. [8]

Peptide microarrays show several advantages over protein microarrays:

Production of a peptide microarray

A peptide microarray is a planar slide with peptides spotted onto it or assembled directly on the surface by in-situ synthesis. Whereas peptides spotted can undergo quality controls that include mass spectrometer analysis and concentration normalization before spotting and result from a single synthetic batch, peptides synthesized directly on the surface may suffer from batch-to-batch variation and limited quality control options. However, peptide synthesis on chip allows the parallel synthesis of tens of thousands of peptides providing larger peptide libraries paired with lower synthesis costs. [9] Peptides are ideally covalently linked through a chemoselective bond leading to peptides with the same orientation for interaction profiling. Some alternative procedures describe unspecific covalent binding and adhesive immobilization.

However, lithographic methods can be used to overcome the problem of excessive number of coupling cycles. Combinatorial synthesis of peptide arrays onto a microchip by laser printing has been described, [9] [10] where a modified colour laser printer is used in combination with conventional solid-phase peptide synthesis chemistry. [11] Amino acids are immobilized within toner particles, and the peptides are printed onto the chip surface in consecutive, combinatorial layers. Melting of the toner upon the start of the coupling reaction ensures that delivery of the amino acids and the coupling reaction can be performed independently. Another advantage of this method is that each amino acid can be produced and purified separately, followed by embedding it into the toner particles, which allows long-term storage.

Applications of peptide microarrays

Peptide microarrays can be used to study different kinds of protein-protein interactions, specially those involving modular protein substructures called peptide recognition modules or, most commonly, protein interaction domains. The reason for this is that such protein substructures recognize short linear motifs often exposed in natively unstructured regions of the binding partner, such that the interaction can be modelled in vitro by peptides as probes and the peptide recognition module as analyte. Most publications can be found in the context of immune monitoring and enzyme profiling.

Immunology


Enzyme profiling

Analysis and evaluation of results

Data analysis and evaluation of results is the most important part of every microarray experiment. [27] After scanning the microarray slides, the scanner records a 20-bit, 16-bit or 8-bit numeric image in tagged image file format (*.tif). The .tif-image enables interpretation and quantification of each fluorescent spot on the scanned microarray slide. This quantitative data is the basis for performing statistical analysis on measured binding events or peptide modifications on the microarray slide. For evaluation and interpretation of detected signals an allocation of the peptide spot (visible in the image) and the corresponding peptide sequence has to be performed. The data for allocation is usually saved in the GenePix Array List (.gal) file and supplied together with the peptide microarray. The .gal-file (a tab-separated text file) can be opened using microarray quantification software-modules or processed with a text editor (e.g. notepad) or Microsoft Excel. This "gal" file is most often provided by the microarray manufacturer and is generated by input txt files and tracking software built into the robots that do the microarray manufacturing.

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Protein</span> Biomolecule consisting of chains of amino acid residues

Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity.

<span class="mw-page-title-main">Proteomics</span> Large-scale study of proteins

Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In addition, other kinds of proteins include antibodies that protect an organism from infection, and hormones that send important signals throughout the body.

<span class="mw-page-title-main">Microarray</span> Small-scale two-dimensional array of samples on a solid support

A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell—that assays (tests) large amounts of biological material using high-throughput screening miniaturized, multiplexed and parallel processing and detection methods. The concept and methodology of microarrays was first introduced and illustrated in antibody microarrays by Tse Wen Chang in 1983 in a scientific publication and a series of patents. The "gene chip" industry started to grow significantly after the 1995 Science Magazine article by the Ron Davis and Pat Brown labs at Stanford University. With the establishment of companies, such as Affymetrix, Agilent, Applied Microarrays, Arrayjet, Illumina, and others, the technology of DNA microarrays has become the most sophisticated and the most widely used, while the use of protein, peptide and carbohydrate microarrays is expanding.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

A protein microarray is a high-throughput method used to track the interactions and activities of proteins, and to determine their function, and determining function on a large scale. Its main advantage lies in the fact that large numbers of proteins can be tracked in parallel. The chip consists of a support surface such as a glass slide, nitrocellulose membrane, bead, or microtitre plate, to which an array of capture proteins is bound. Probe molecules, typically labeled with a fluorescent dye, are added to the array. Any reaction between the probe and the immobilised protein emits a fluorescent signal that is read by a laser scanner. Protein microarrays are rapid, automated, economical, and highly sensitive, consuming small quantities of samples and reagents. The concept and methodology of protein microarrays was first introduced and illustrated in antibody microarrays in 1983 in a scientific publication and a series of patents. The high-throughput technology behind the protein microarray was relatively easy to develop since it is based on the technology developed for DNA microarrays, which have become the most widely used microarrays.

<span class="mw-page-title-main">Chemical biology</span> Scientific discipline

Chemical biology is a scientific discipline between the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. Although often confused with biochemistry, which studies the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology remains distinct by focusing on the application of chemical tools to address biological questions.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.

Protein tags are peptide sequences genetically grafted onto a recombinant protein. Tags are attached to proteins for various purposes. They can be added to either end of the target protein, so they are either C-terminus or N-terminus specific or are both C-terminus and N-terminus specific. Some tags are also inserted at sites within the protein of interest; they are known as internal tags.

Bacterial display is a protein engineering technique used for in vitro protein evolution. Libraries of polypeptides displayed on the surface of bacteria can be screened using flow cytometry or iterative selection procedures (biopanning). This protein engineering technique allows us to link the function of a protein with the gene that encodes it. Bacterial display can be used to find target proteins with desired properties and can be used to make affinity ligands which are cell-specific. This system can be used in many applications including the creation of novel vaccines, the identification of enzyme substrates and finding the affinity of a ligand for its target protein.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

<span class="mw-page-title-main">Antibody microarray</span> Form of protein microarray

An antibody microarray is a specific form of protein microarray. In this technology, a collection of captured antibodies are spotted and fixed on a solid surface such as glass, plastic, membrane, or silicon chip, and the interaction between the antibody and its target antigen is detected. Antibody microarrays are often used for detecting protein expression from various biofluids including serum, plasma and cell or tissue lysates. Antibody arrays may be used for both basic research and medical and diagnostic applications.

Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.

<span class="mw-page-title-main">Immunoproteomics</span> Study of large set of protein

Immunoproteomics is the study of large sets of proteins (proteomics) involved in the immune response.

2F5 is a broadly neutralizing human monoclonal antibody (mAb) that has been shown to bind to and neutralize HIV-1 in vitro, making it a potential candidate for use in vaccine synthesis. 2F5 recognizes an epitope in the membrane-proximal external region (MPER) of HIV-1 gp41. 2F5 then binds to this epitope and its constant region interacts with the viral lipid membrane, which neutralizes the virus.

Immunosignaturing is a medical diagnostic test which uses arrays of random-sequence peptides to associate antibodies in a blood sample with a disease.

Computational Resources for Drug Discovery (CRDD) is an important module of the in silico module of Open Source for Drug Discovery (OSDD). The CRDD web portal provides computer resources related to drug discovery, predicting inhibitors, and predicting the ADME-Tox properties of molecules on a single platform. It caters to researchers researching computer-aided drug design by providing computational resources, and hosting a discussion forum. One of the major objectives of CRDD is to promote open source software in the field of cheminformatics and pharmacoinformatics.

<span class="mw-page-title-main">Bio-layer interferometry</span> Optical biosensing technology

Bio-layer interferometry (BLI) is an optical biosensing technology that analyzes biomolecular interactions in real-time without the need for fluorescent labeling. Alongside Surface Plasmon Resonance, BLI is one of few widely available label-free biosensing technologies, a detection style that yields more information in less time than traditional processes. The technology relies on the phase shift-wavelength correlation created between interference patterns off of two unique surfaces on the tip of a biosensor. BLI has significant applications in quantifying binding strength, measuring protein interactions, and identifying properties of reaction kinetics, such as rate constants and reaction rates.

Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail.

References

  1. ↑ Hansen, Lajla Bruntse; Buus, Soren; Schafer-Nielsen, Claus (2013-07-23). "Identification and Mapping of Linear Antibody Epitopes in Human Serum Albumin Using High-Density Peptide Arrays". PLOS ONE. 8 (7): e68902. Bibcode:2013PLoSO...868902H. doi: 10.1371/journal.pone.0068902 . ISSN   1932-6203. PMC   3720873 . PMID   23894373.
  2. ↑ Panse, S; Dong, L; Burian, A; Carus, R; Schutkowski, M; Reimer, U; Schneider-Mergener, J (2004). "Profiling of generic anti-phosphopeptide antibodies and kinases with peptide microarrays using radioactive and fluorescence-based assays". Molecular Diversity. 8 (3): 291–9. doi:10.1023/B:MODI.0000036240.39384.eb. PMID   15384422. S2CID   407457.
  3. ↑ Kaeberlein, Matt; McDonagh, Thomas; Heltweg, Birgit; Hixon, Jeffrey; Westman, Eric A.; Caldwell, Seth D.; Napper, Andrew; Curtis, Rory; DiStefano, Peter S. (2005-04-29). "Substrate-specific Activation of Sirtuins by Resveratrol". Journal of Biological Chemistry. 280 (17): 17038–17045. doi: 10.1074/jbc.M500655200 . ISSN   0021-9258. PMID   15684413.
  4. ↑ Fernández Gavela, Adrián; Grajales García, Daniel; Ramirez, Jhonattan C.; Lechuga, Laura M. (2016-02-24). "Last Advances in Silicon-Based Optical Biosensors". Sensors. 16 (3): 285. Bibcode:2016Senso..16..285F. doi: 10.3390/s16030285 . PMC   4813860 . PMID   26927105.
  5. ↑ Fang, Ye (2010). "Resonant Waveguide Grating Biosensor for Microarrays". Optical Guided-wave Chemical and Biosensors II. Springer Series on Chemical Sensors and Biosensors. Vol. 8. Springer, Berlin, Heidelberg. pp. 27–42. doi:10.1007/978-3-642-02827-4_2. ISBN   9783642028267.
  6. ↑ Picaud, Sarah; Filippakopoulos, Panagis (2015-08-17). "SPOTing Acetyl-Lysine Dependent Interactions". Microarrays. 4 (3): 370–388. doi: 10.3390/microarrays4030370 . PMC   4996381 . PMID   27600229.
  7. ↑ Hundsberger, Harald; Önder, Kamil; Schuller-Götzburg, Peter; Virok, Dezso P.; Herzog, Julia; Rid, Raphaela (2017-06-08). "Assembly and use of high-density recombinant peptide chips for large-scale ligand screening is a practical alternative to synthetic peptide libraries". BMC Genomics. 18 (1): 450. doi: 10.1186/s12864-017-3814-3 . ISSN   1471-2164. PMC   5463365 . PMID   28595602.
  8. ↑ Szymczak, Lindsey C.; Kuo, Hsin-Yu; Mrksich, Milan (2018-01-02). "Peptide Arrays: Development and Application". Analytical Chemistry. 90 (1): 266–282. doi:10.1021/acs.analchem.7b04380. ISSN   0003-2700. PMC   6526727 . PMID   29135227.
  9. 1 2 Beyer, M; Nesterov, A; Block, I; König, K; Felgenhauer, T; Fernandez, S; Leibe, K; Torralba, G; Hausmann, M; Trunk, U; Lindenstruth, V; Bischoff, FR; Stadler, V; Breitling, F (Dec 21, 2007). "Combinatorial synthesis of peptide arrays onto a microchip". Science. 318 (5858): 1888. Bibcode:2007Sci...318.1888B. doi:10.1126/science.1149751. PMID   18096799. S2CID   33941406.
  10. ↑ Breitling, Frank; Felgenhauer, Thomas; Nesterov, Alexander; Lindenstruth, Volker; Stadler, Volker; Bischoff, F. Ralf (2009-03-23). "Particle-Based Synthesis of Peptide Arrays". ChemBioChem. 10 (5): 803–808. doi:10.1002/cbic.200800735. ISSN   1439-7633. PMID   19191248. S2CID   13173295.
  11. ↑ Stadler, Volker; Felgenhauer, Thomas; Beyer, Mario; Fernandez, Simon; Leibe, Klaus; Güttler, Stefan; Gröning, Martin; König, Kai; Torralba, Gloria (2008-09-01). "Combinatorial Synthesis of Peptide Arrays with a Laser Printer". Angewandte Chemie International Edition. 47 (37): 7132–7135. doi:10.1002/anie.200801616. ISSN   1521-3773. PMID   18671222.
  12. ↑ Zandian, Arash; Forsström, Björn; Häggmark-Månberg, Anna; Schwenk, Jochen M.; Uhlén, Mathias; Nilsson, Peter; Ayoglu, Burcu (9 February 2017). "Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy". Journal of Proteome Research. 16 (3): 1300–1314. doi: 10.1021/acs.jproteome.6b00916 . PMID   28121444.
  13. ↑ Lin, Jing; Bardina, Ludmilla; Shreffler, Wayne G.; Andreae, Doerthe A.; Ge, Yongchao; Wang, Julie; Bruni, Francesca M.; Fu, Zhiyan; et al. (2009). "Development of a novel peptide microarray for large-scale epitope mapping of food allergens". Journal of Allergy and Clinical Immunology. 124 (2): 315–22, 322.e1–3. doi:10.1016/j.jaci.2009.05.024. PMC   2757036 . PMID   19577281.
  14. ↑ Linnebacher, M; Lorenz, P; Koy, C; Jahnke, A; Born, N; Steinbeck, F; Wollbold, J; Latzkow, T; et al. (2012). "Clonality characterization of natural epitope-specific antibodies against the tumor-related antigen topoisomerase IIa by peptide chip and proteome analysis: A pilot study with colorectal carcinoma patient samples". Analytical and Bioanalytical Chemistry. 403 (1): 227–38. doi:10.1007/s00216-012-5781-5. PMID   22349330. S2CID   33847079.
  15. ↑ Jaenisch, Thomas; Heiss, Kirsten; Fischer, Nico; Geiger, Carolin; Bischoff, F. Ralf; Moldenhauer, Gerhard; Rychlewski, Leszek; Sié, Ali; Coulibaly, Boubacar (April 2019). "High-density Peptide Arrays Help to Identify Linear Immunogenic B-cell Epitopes in Individuals Naturally Exposed to Malaria Infection". Molecular & Cellular Proteomics. 18 (4): 642–656. doi: 10.1074/mcp.RA118.000992 . ISSN   1535-9484. PMC   6442360 . PMID   30630936.
  16. ↑ Callaway, Ewen (2011). "Clues emerge to explain first successful HIV vaccine trial". Nature. doi:10.1038/news.2011.541.
  17. ↑ Heiss, Kirsten; Heidepriem, Jasmin; Fischer, Nico; Weber, Laura K.; Dahlke, Christine; Jaenisch, Thomas; Loeffler, Felix F. (September 2020). "Rapid Response to Pandemic Threats: Immunogenic Epitope Detection of Pandemic Pathogens for Diagnostics and Vaccine Development Using Peptide Microarrays". Journal of Proteome Research. doi:10.1021/acs.jproteome.0c00484.{{cite journal}}: CS1 maint: date and year (link)
  18. ↑ Garren, H; Robinson, WH; Krasulová, E; Havrdová, E; Nadj, C; Selmaj, K; Losy, J; Nadj, I; et al. (2008). "Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis". Annals of Neurology. 63 (5): 611–20. CiteSeerX   10.1.1.418.3083 . doi:10.1002/ana.21370. PMID   18481290. S2CID   16111674.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  19. ↑ Gaseitsiwe, S.; Valentini, D.; Mahdavifar, S.; Reilly, M.; Ehrnst, A.; Maeurer, M. (2009). "Peptide Microarray-Based Identification of Mycobacterium tuberculosis Epitope Binding to HLA-DRB1*0101, DRB1*1501, and DRB1*0401". Clinical and Vaccine Immunology. 17 (1): 168–75. doi:10.1128/CVI.00208-09. PMC   2812096 . PMID   19864486.
  20. ↑ Weber, Laura K.; Palermo, Andrea; Kügler, Jonas; Armant, Olivier; Isse, Awale; Rentschler, Simone; Jaenisch, Thomas; Hubbuch, Jürgen; Dübel, Stefan (April 2017). "Single amino acid fingerprinting of the human antibody repertoire with high density peptide arrays". Journal of Immunological Methods. 443: 45–54. doi:10.1016/j.jim.2017.01.012. ISSN   1872-7905. PMID   28167275.
  21. ↑ Tomaras, GD; Binley, JM; Gray, ES; Crooks, ET; Osawa, K; Moore, PL; Tumba, N; Tong, T; et al. (2011). "Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals". Journal of Virology. 85 (21): 11502–19. doi:10.1128/JVI.05363-11. PMC   3194956 . PMID   21849452.
  22. ↑ Kindrachuk, J; Arsenault, R; Kusalik, T; Kindrachuk, KN; Trost, B; Napper, S; Jahrling, PB; Blaney, JE (2011). "Systems kinomics demonstrates congo basin monkeypox virus infection selectively modulates host cell signaling responses as compared to West African monkeypox virus". Molecular & Cellular Proteomics. 11 (6): M111.015701. doi: 10.1074/mcp.M111.015701 . PMC   3433897 . PMID   22205724.
  23. ↑ Lizcano, J. M.; Deak, M; Morrice, N; Kieloch, A; Hastie, CJ; Dong, L; Schutkowski, M; Reimer, U; Alessi, DR (2002). "Molecular Basis for the Substrate Specificity of NIMA-related Kinase-6 (NEK6). EVIDENCE THAT NEK6 DOES NOT PHOSPHORYLATE THE HYDROPHOBIC MOTIF OF RIBOSOMAL S6 PROTEIN KINASE AND SERUM- AND GLUCOCORTICOID-INDUCED PROTEIN KINASE IN VIVO". Journal of Biological Chemistry. 277 (31): 27839–49. doi: 10.1074/jbc.M202042200 . PMID   12023960.
  24. ↑ Delgado, J. Y.; Coba, M.; Anderson, C. N. G.; Thompson, K. R.; Gray, E. E.; Heusner, C. L.; Martin, K. C.; Grant, S. G. N.; O'Dell, T. J. (2007). "NMDA Receptor Activation Dephosphorylates AMPA Receptor Glutamate Receptor 1 Subunits at Threonine 840". Journal of Neuroscience. 27 (48): 13210–21. doi:10.1523/JNEUROSCI.3056-07.2007. PMC   2851143 . PMID   18045915.
  25. ↑ Thiele, A; Krentzlin, K; Erdmann, F; Rauh, D; Hause, G; Zerweck, J; Kilka, S; Pösel, S; et al. (2011). "Parvulin 17 promotes microtubule assembly by its peptidyl-prolyl cis/trans isomerase activity". Journal of Molecular Biology. 411 (4): 896–909. doi:10.1016/j.jmb.2011.06.040. PMID   21756916.
  26. ↑ Parsons, LS; Wilkens, S (2012). "Probing subunit-subunit interactions in the yeast vacuolar ATPase by peptide arrays". PLOS ONE. 7 (10): e46960. Bibcode:2012PLoSO...746960P. doi: 10.1371/journal.pone.0046960 . PMC   3470569 . PMID   23071676.
  27. ↑ Hecker, M; Lorenz, P; Steinbeck, F; Hong, L; Riemekasten, G; Li, Y; Zettl, UK; Thiesen, HJ (2012). "Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis". Autoimmunity Reviews. 11 (3): 180–90. doi:10.1016/j.autrev.2011.05.010. PMID   21621003.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.