WW domain

Last updated
WW domain
PDB 1pin EBI.jpg
Structure of the human mitotic rotamase Pin1. [1]
Identifiers
SymbolWW
Pfam PF00397
InterPro IPR001202
PROSITE PDOC50020
SCOP2 1pin / SCOPe / SUPFAM
CDD cd00201
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

The WW domain [2] (also known as the rsp5-domain [3] or WWP repeating motif [4] ) is a modular protein domain that mediates specific interactions with protein ligands. This domain is found in a number of unrelated signaling and structural proteins and may be repeated up to four times in some proteins. [2] [3] [4] [5] Apart from binding preferentially to proteins that are proline-rich, with particular proline-motifs, [AP]-P-P-[AP]-Y, some WW domains bind to phosphoserine- and phosphothreonine-containing motifs. [6]

Contents

Structure and ligands

The WW domain is one of the smallest protein modules, composed of only 40 amino acids, which mediates specific protein-protein interactions with short proline-rich or proline-containing motifs. [6] Named after the presence of two conserved tryptophans (W), which are spaced 20-22 amino acids apart within the sequence, [2] the WW domain folds into a meandering triple-stranded beta sheet. [7] The identification of the WW domain was facilitated by the analysis of two splice isoforms of YAP gene product, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids. These extra amino acids are encoded by a spliced-in exon and represent the second WW domain in YAP1-2 isoform. [2] [8]

The first structure of the WW domain was determined in solution by NMR approach. [7] It represented the WW domain of human YAP in complex with peptide ligand containing Proline-Proline-x–Tyrosine (PPxY where x = any amino acid) consensus motif. [6] [7] Recently, the YAP WW domain structure in complex with SMAD-derived, PPxY motif-containing peptide was further refined. [9] Apart from the PPxY motif, certain WW domains recognize LPxY motif (where L is Leucine), [10] and several WW domains bind to phospho-Serine-Proline (p-SP) or phospho-Threonine-Proline (p-TP) motifs in a phospho-dependent manner. [11] Structures of these WW domain complexes confirmed molecular details of phosphorylation-regulated interactions. [1] [12] There are also WW domains that interact with polyprolines that are flanked by arginine residues or interrupted by leucine residues, but they do not contain aromatic amino acids. [13] [14]

Signaling function

The WW domain is known to mediate regulatory protein complexes in various signaling networks, including the Hippo signaling pathway. [15] The importance of WW domain-mediated complexes in signaling was underscored by the characterization of genetic syndromes that are caused by loss-of-function point mutations in the WW domain or its cognate ligand. These syndromes are Golabi-Ito-Hall syndrome of intellectual disability caused by missense mutation in a WW domain [16] [17] and Liddle syndrome of hypertension caused by point mutations within PPxY motif. [18] [19]

Examples

A large variety of proteins containing the WW domain are known. These include; dystrophin, a multidomain cytoskeletal protein; utrophin, a dystrophin-like protein; vertebrate YAP protein, substrate of LATS1 and LATS2 serine-threonine kinases of the Hippo tumor suppressor pathway; Mus musculus (Mouse) NEDD4, involved in the embryonic development and differentiation of the central nervous system; Saccharomyces cerevisiae (Baker's yeast) RSP5, similar to NEDD4 in its molecular organization; Rattus norvegicus (Rat) FE65, a transcription-factor activator expressed preferentially in brain; Nicotiana tabacum (Common tobacco) DB10 protein, amongst others. [20]

In 2004, the first comprehensive protein-peptide interaction map for a human modular domain was reported using individually expressed WW domains and genome predicted, PPxY-containing synthetic peptides. [21] At present in the human proteome, 98 WW domains [22] and more than 2000 PPxY-containing peptides, [17] have been identified from sequence analysis of the genome.

Inhibitor

YAP is a WW domain-containing protein that functions as a potent oncogene. [2] [23] Its WW domains must be intact for YAP to act as a transcriptional co-activator that induces expression of proliferative genes. [24] Recent study has shown that endohedral metallofullerenol, a compound that was originally developed as a contrasting agent for MRI (magnetic resonance imaging), has antineoplastic properties. [25] Via molecular dynamic simulations, the ability of this compound to outcompete proline-rich peptides and bind effectively to the WW domain of YAP was documented. [26] Endohedral metallofullerenol may represent a lead compound for the development of therapies for cancer patients who harbor amplified or overexpressed YAP. [26] [27]

In the study of protein folding

Because of its small size and well-defined structure, the WW domain was developed by the Gruebele and Kelly groups into a favorite subject of protein folding studies. [28] [29] [30] [31] [32] Among these studies, the work of Rama Ranganathan [33] [34] and David E. Shaw are also notable. [35] [36] Ranganathan’s team has shown that a simple statistical energy function, which identifies co-evolution between amino acid residues within the WW domain, is necessary and sufficient to specify sequence that folds into native structure. [34] Using such an algorithm, he and his team synthesized libraries of artificial WW domains that functioned in a very similar manner to their natural counterparts, recognizing class-specific proline-rich ligand peptides, [33] The Shaw laboratory developed a specialized machine that allowed elucidation of the atomic level behavior of the WW domain on a biologically relevant time scale. [35] He and his team employed equilibrium simulations of a WW domain and identified seven unfolding and eight folding events. [36]

Being relatively short, 30 to 35 amino acids long, WW domain is amenable to chemical synthesis. It is cooperatively folded and can host chemically introduced non-canonical amino acids. Based on these properties, WW domain has been shown to be a versatile platform for the chemical interrogation of intramolecular interactions and conformational propensities in folded proteins. [37]

Related Research Articles

<span class="mw-page-title-main">Alpha helix</span> Type of secondary structure of proteins

The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earlier along the protein sequence.

<span class="mw-page-title-main">Beta sheet</span> Protein structural motif

The beta sheet, (β-sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, notably Alzheimer's disease.

Collagen is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of amino acids bound together to form a triple helix of elongated fibril known as a collagen helix. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin.

<span class="mw-page-title-main">SH3 domain</span> Small protein domain found in some kinases and GTPases

The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.

Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group -NH
2 but is rather a secondary amine. The secondary amine nitrogen is in the protonated form (NH2+) under biological conditions, while the carboxyl group is in the deprotonated −COO− form. The "side chain" from the α carbon connects to the nitrogen forming a pyrrolidine loop, classifying it as a aliphatic amino acid. It is non-essential in humans, meaning the body can synthesize it from the non-essential amino acid L-glutamate. It is encoded by all the codons starting with CC (CCU, CCC, CCA, and CCG).

<span class="mw-page-title-main">Protein structure prediction</span> Type of biological prediction

Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its secondary and tertiary structure from primary structure. Structure prediction is different from the inverse problem of protein design. Protein structure prediction is one of the most important goals pursued by computational biology; and it is important in medicine and biotechnology.

<span class="mw-page-title-main">Ramachandran plot</span> Visual representation of allowable protein conformations

In biochemistry, a Ramachandran plot, originally developed in 1963 by G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan, is a way to visualize energetically allowed regions for backbone dihedral angles ψ against φ of amino acid residues in protein structure. The figure on the left illustrates the definition of the φ and ψ backbone dihedral angles. The ω angle at the peptide bond is normally 180°, since the partial-double-bond character keeps the peptide bond planar. The figure in the top right shows the allowed φ,ψ backbone conformational regions from the Ramachandran et al. 1963 and 1968 hard-sphere calculations: full radius in solid outline, reduced radius in dashed, and relaxed tau (N-Cα-C) angle in dotted lines. Because dihedral angle values are circular and 0° is the same as 360°, the edges of the Ramachandran plot "wrap" right-to-left and bottom-to-top. For instance, the small strip of allowed values along the lower-left edge of the plot are a continuation of the large, extended-chain region at upper left.

<span class="mw-page-title-main">Protein structure</span> Three-dimensional arrangement of atoms in an amino acid-chain molecule

Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers – specifically polypeptides – formed from sequences of amino acids, the monomers of the polymer. A single amino acid monomer may also be called a residue indicating a repeating unit of a polymer. Proteins form by amino acids undergoing condensation reactions, in which the amino acids lose one water molecule per reaction in order to attach to one another with a peptide bond. By convention, a chain under 30 amino acids is often identified as a peptide, rather than a protein. To be able to perform their biological function, proteins fold into one or more specific spatial conformations driven by a number of non-covalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces, and hydrophobic packing. To understand the functions of proteins at a molecular level, it is often necessary to determine their three-dimensional structure. This is the topic of the scientific field of structural biology, which employs techniques such as X-ray crystallography, NMR spectroscopy, cryo-electron microscopy (cryo-EM) and dual polarisation interferometry to determine the structure of proteins.

<span class="mw-page-title-main">Beta hairpin</span>

The beta hairpin is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in an antiparallel direction, and linked by a short loop of two to five amino acids. Beta hairpins can occur in isolation or as part of a series of hydrogen bonded strands that collectively comprise a beta sheet.

<span class="mw-page-title-main">Cyclotide</span> Disulfide-rich ring peptides found in plants

In biochemistry, cyclotides are small, disulfide-rich peptides isolated from plants. Typically containing 28-37 amino acids, they are characterized by their head-to-tail cyclised peptide backbone and the interlocking arrangement of their three disulfide bonds. These combined features have been termed the cyclic cystine knot (CCK) motif. To date, over 100 cyclotides have been isolated and characterized from species of the families Rubiaceae, Violaceae, and Cucurbitaceae. Cyclotides have also been identified in agriculturally important families such as the Fabaceae and Poaceae.

<span class="mw-page-title-main">YAP1</span> Protein-coding gene in the species Homo sapiens

YAP1, also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. YAP1 is a potent oncogene, which is amplified in various human cancers.

<span class="mw-page-title-main">PRPF40A</span> Protein-coding gene in the species Homo sapiens

Pre-mRNA-processing factor 40 homolog A is a protein that in humans is encoded by the PRPF40A gene.

<span class="mw-page-title-main">PRB1</span> Protein-coding gene in the species Homo sapiens

Basic salivary proline-rich protein 1 is a protein that in humans is encoded by the PRB1 gene.

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

WW domain-containing adapter protein with coiled-coil is a protein that in humans is encoded by the WAC gene.

<span class="mw-page-title-main">WBP2</span> Protein-coding gene in the species Homo sapiens

WW domain-binding protein 2 is a protein that in humans is encoded by the WBP2 gene.

<span class="mw-page-title-main">WBP4</span> Protein-coding gene in the species Homo sapiens

WW domain-binding protein 4 is a protein that in humans is encoded by the WBP4 gene.

<span class="mw-page-title-main">WBP1</span> Protein-coding gene in the species Homo sapiens

WW domain-binding protein 1 is a protein that in humans is encoded by the WBP1 gene.

<span class="mw-page-title-main">Short linear motif</span>

In molecular biology short linear motifs (SLiMs), linear motifs or minimotifs are short stretches of protein sequence that mediate protein–protein interaction.

WH1 domain is an evolutionary conserved protein domain. Therefore, it has an important function.

<span class="mw-page-title-main">Elongation factor P</span>

EF-P is an essential protein that in bacteria stimulates the formation of the first peptide bonds in protein synthesis. Studies show that EF-P prevents ribosomes from stalling during the synthesis of proteins containing consecutive prolines. EF-P binds to a site located between the binding site for the peptidyl tRNA and the exiting tRNA. It spans both ribosomal subunits with its amino-terminal domain positioned adjacent to the aminoacyl acceptor stem and its carboxyl-terminal domain positioned next to the anticodon stem-loop of the P site-bound initiator tRNA. The EF-P protein shape and size is very similar to a tRNA and interacts with the ribosome via the exit “E” site on the 30S subunit and the peptidyl-transferase center (PTC) of the 50S subunit. EF-P is a translation aspect of an unknown function, therefore It probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity as acceptors for peptidyl transferase.

References

  1. 1 2 PDB: 1PIN ​; Ranganathan R, Lu KP, Hunter T, Noel JP (June 1997). "Structural and functional analysis of the mitotic rotamase Pin1 suggests substrate recognition is phosphorylation dependent". Cell. 89 (6): 875–86. doi: 10.1016/S0092-8674(00)80273-1 . PMID   9200606. S2CID   16219532.
  2. 1 2 3 4 5 Bork P, Sudol M (December 1994). "The WW domain: a signalling site in dystrophin?". Trends in Biochemical Sciences. 19 (12): 531–3. doi:10.1016/0968-0004(94)90053-1. PMID   7846762.
  3. 1 2 Hofmann K, Bucher P (January 1995). "The rsp5-domain is shared by proteins of diverse functions". FEBS Letters. 358 (2): 153–7. doi: 10.1016/0014-5793(94)01415-W . PMID   7828727. S2CID   23110605.
  4. 1 2 André B, Springael JY (December 1994). "WWP, a new amino acid motif present in single or multiple copies in various proteins including dystrophin and the SH3-binding Yes-associated protein YAP65". Biochemical and Biophysical Research Communications. 205 (2): 1201–5. doi:10.1006/bbrc.1994.2793. PMID   7802651.
  5. ↑ Sudol M, Chen HI, Bougeret C, Einbond A, Bork P (August 1995). "Characterization of a novel protein-binding module--the WW domain". FEBS Letters. 369 (1): 67–71. doi: 10.1016/0014-5793(95)00550-S . PMID   7641887. S2CID   20664267.
  6. 1 2 3 Chen HI, Sudol M (August 1995). "The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules". Proceedings of the National Academy of Sciences of the United States of America. 92 (17): 7819–23. Bibcode:1995PNAS...92.7819C. doi: 10.1073/pnas.92.17.7819 . PMC   41237 . PMID   7644498.
  7. 1 2 3 Macias MJ, Hyvönen M, Baraldi E, Schultz J, Sudol M, Saraste M, Oschkinat H (August 1996). "Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide". Nature. 382 (6592): 646–9. Bibcode:1996Natur.382..646M. doi:10.1038/382646a0. PMID   8757138. S2CID   4306964.
  8. ↑ Sudol M, Bork P, Einbond A, Kastury K, Druck T, Negrini M, Huebner K, Lehman D (June 1995). "Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain". The Journal of Biological Chemistry. 270 (24): 14733–41. doi: 10.1074/jbc.270.24.14733 . PMID   7782338.
  9. ↑ Aragón E, Goerner N, Xi Q, Gomes T, Gao S, Massagué J, Macias MJ (October 2012). "Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways". Structure. 20 (10): 1726–36. doi:10.1016/j.str.2012.07.014. PMC   3472128 . PMID   22921829.
  10. ↑ Bruce MC, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D (October 2008). "Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain". The Biochemical Journal. 415 (1): 155–63. doi:10.1042/BJ20071708. PMID   18498246.
  11. ↑ Lu PJ, Zhou XZ, Shen M, Lu KP (February 1999). "Function of WW domains as phosphoserine- or phosphothreonine-binding modules". Science. 283 (5406): 1325–8. Bibcode:1999Sci...283.1325L. doi:10.1126/science.283.5406.1325. PMID   10037602.
  12. ↑ Verdecia MA, Bowman ME, Lu KP, Hunter T, Noel JP (August 2000). "Structural basis for phosphoserine-proline recognition by group IV WW domains". Nature Structural Biology. 7 (8): 639–43. doi:10.1038/77929. PMID   10932246. S2CID   20088089.
  13. ↑ Bedford MT, Sarbassova D, Xu J, Leder P, Yaffe MB (April 2000). "A novel pro-Arg motif recognized by WW domains". The Journal of Biological Chemistry. 275 (14): 10359–69. doi: 10.1074/jbc.275.14.10359 . PMID   10744724.
  14. ↑ Ermekova KS, Zambrano N, Linn H, Minopoli G, Gertler F, Russo T, Sudol M (December 1997). "The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled". The Journal of Biological Chemistry. 272 (52): 32869–77. doi: 10.1074/jbc.272.52.32869 . PMID   9407065.
  15. ↑ Sudol M, Harvey KF (November 2010). "Modularity in the Hippo signaling pathway". Trends in Biochemical Sciences. 35 (11): 627–33. doi:10.1016/j.tibs.2010.05.010. PMID   20598891.
  16. ↑ Lubs H, Abidi FE, Echeverri R, Holloway L, Meindl A, Stevenson RE, Schwartz CE (June 2006). "Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene". Journal of Medical Genetics. 43 (6): e30. doi:10.1136/jmg.2005.037556. PMC   2564547 . PMID   16740914.
  17. 1 2 Tapia VE, Nicolaescu E, McDonald CB, Musi V, Oka T, Inayoshi Y, Satteson AC, Mazack V, Humbert J, Gaffney CJ, Beullens M, Schwartz CE, Landgraf C, Volkmer R, Pastore A, Farooq A, Bollen M, Sudol M (June 2010). "Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1 affects its binding activity and deregulates pre-mRNA splicing". The Journal of Biological Chemistry. 285 (25): 19391–401. doi: 10.1074/jbc.M109.084525 . PMC   2885219 . PMID   20410308.
  18. ↑ Schild L, Lu Y, Gautschi I, Schneeberger E, Lifton RP, Rossier BC (May 1996). "Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome". The EMBO Journal. 15 (10): 2381–7. doi:10.1002/j.1460-2075.1996.tb00594.x. PMC   450168 . PMID   8665845.
  19. ↑ Staub O, Gautschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, Rotin D (November 1997). "Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination". The EMBO Journal. 16 (21): 6325–36. doi:10.1093/emboj/16.21.6325. PMC   1170239 . PMID   9351815.
  20. ↑ InterPro :  IPR001202
  21. ↑ Hu H, Columbus J, Zhang Y, Wu D, Lian L, Yang S, Goodwin J, Luczak C, Carter M, Chen L, James M, Davis R, Sudol M, Rodwell J, Herrero JJ (March 2004). "A map of WW domain family interactions". Proteomics. 4 (3): 643–55. doi:10.1002/pmic.200300632. PMID   14997488. S2CID   1656676.
  22. ↑ Sudol M, McDonald CB, Farooq A (August 2012). "Molecular insights into the WW domain of the Golabi-Ito-Hall syndrome protein PQBP1". FEBS Letters. 586 (17): 2795–9. doi:10.1016/j.febslet.2012.03.041. PMC   3413755 . PMID   22710169.
  23. ↑ Huang J, Wu S, Barrera J, Matthews K, Pan D (August 2005). "The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP". Cell. 122 (3): 421–34. doi: 10.1016/j.cell.2005.06.007 . PMID   16096061. S2CID   14139806.
  24. ↑ Zhao B, Kim J, Ye X, Lai ZC, Guan KL (February 2009). "Both TEAD-binding and WW domains are required for the growth stimulation and oncogenic transformation activity of yes-associated protein". Cancer Research. 69 (3): 1089–98. doi: 10.1158/0008-5472.CAN-08-2997 . PMID   19141641.
  25. ↑ Kang SG, Zhou G, Yang P, Liu Y, Sun B, Huynh T, Meng H, Zhao L, Xing G, Chen C, Zhao Y, Zhou R (September 2012). "Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine". Proceedings of the National Academy of Sciences of the United States of America. 109 (38): 15431–6. Bibcode:2012PNAS..10915431K. doi: 10.1073/pnas.1204600109 . PMC   3458392 . PMID   22949663.
  26. 1 2 Kang SG, Huynh T, Zhou R (2012). "Non-destructive inhibition of metallofullerenol Gd@C(82)(OH)(22) on WW domain: implication on signal transduction pathway". Scientific Reports. 2: 957. Bibcode:2012NatSR...2E.957K. doi:10.1038/srep00957. PMC   3518810 . PMID   23233876.
  27. ↑ Sudol M, Shields DC, Farooq A (September 2012). "Structures of YAP protein domains reveal promising targets for development of new cancer drugs". Seminars in Cell & Developmental Biology. 23 (7): 827–33. doi:10.1016/j.semcdb.2012.05.002. PMC   3427467 . PMID   22609812.
  28. ↑ Crane, JC, Koepf, EK, Kelly, JW, Gruebele M (April 2000). "Mapping the Transition State of the WW Domain Beta-Sheet". Journal of Molecular Biology. 298 (2): 283–92. doi:10.1006/jmbi.2000.3665. PMID   10764597.
  29. ↑ Jäger, M, Nguyen, H, Crane, JC, Kelly, JW, Gruebele M (August 2001). "The Folding Mechanism of a Beta-Sheet: The WW Domain". Journal of Molecular Biology. 311 (2): 373–93. doi:10.1006/jmbi.2001.4873. PMID   11478867.
  30. ↑ Fuller AA, Du D, Liu F, Davoren JE, Bhabha G, Kroon G, Case DA, Dyson HJ, Powers ET, Wipf P, Gruebele M, Kelly JW (July 2009). "Evaluating beta-turn mimics as beta-sheet folding nucleators". Proceedings of the National Academy of Sciences of the United States of America. 106 (27): 11067–72. Bibcode:2009PNAS..10611067F. doi: 10.1073/pnas.0813012106 . PMC   2708776 . PMID   19541614.
  31. ↑ Jager M, Deechongkit S, Koepf EK, Nguyen H, Gao J, Powers ET, Gruebele M, Kelly JW (2008). "Understanding the mechanism of beta-sheet folding from a chemical and biological perspective". Biopolymers. 90 (6): 751–8. doi:10.1002/bip.21101. PMID   18844292.
  32. ↑ Jäger M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW (July 2006). "Structure-function-folding relationship in a WW domain". Proceedings of the National Academy of Sciences of the United States of America. 103 (28): 10648–53. Bibcode:2006PNAS..10310648J. doi: 10.1073/pnas.0600511103 . PMC   1502286 . PMID   16807295.
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  34. 1 2 Socolich M, Lockless SW, Russ WP, Lee H, Gardner KH, Ranganathan R (September 2005). "Evolutionary information for specifying a protein fold". Nature. 437 (7058): 512–8. Bibcode:2005Natur.437..512S. doi:10.1038/nature03991. PMID   16177782. S2CID   4363255.
  35. 1 2 Piana S, Sarkar K, Lindorff-Larsen K, Guo M, Gruebele M, Shaw DE (January 2011). "Computational design and experimental testing of the fastest-folding β-sheet protein". Journal of Molecular Biology. 405 (1): 43–8. doi:10.1016/j.jmb.2010.10.023. PMID   20974152.
  36. 1 2 Shaw DE, Maragakis P, Lindorff-Larsen K, Piana S, Dror RO, Eastwood MP, Bank JA, Jumper JM, Salmon JK, Shan Y, Wriggers W (October 2010). "Atomic-level characterization of the structural dynamics of proteins". Science. 330 (6002): 341–6. Bibcode:2010Sci...330..341S. doi:10.1126/science.1187409. PMID   20947758. S2CID   3495023.
  37. ↑ Ardejani MS, Powers ET, Kelly JW (August 2017). "Using Cooperatively Folded Peptides To Measure Interaction Energies and Conformational Propensities". Accounts of Chemical Research. 50 (8): 1875–1882. doi:10.1021/acs.accounts.7b00195. PMC   5584629 . PMID   28723063.
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