A map of WW domain family interactions

WW domains are protein modules that bind proline‐rich ligands. WW domain‐ligand complexes are of importance as they have been implicated in several human diseases such as muscular dystrophy, cancer, hypertension, Alzheimer's, and Huntington's diseases. We report the results of a protein ar...

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Bibliographic Details
Published in:	Proteomics (Weinheim) Vol. 4; no. 3; pp. 643 - 655
Main Authors:	Hu, Hai, Columbus, John, Zhang, Yi, Wu, Dongying, Lian, Lubing, Yang, Song, Goodwin, Jennifer, Luczak, Christine, Carter, Mark, Chen, Lin, James, Michael, Davis, Roger, Sudol, Marius, Rodwell, John, Herrero, Juan J.
Format:	Journal Article
Language:	English
Published:	Weinheim WILEY-VCH Verlag 01-03-2004 WILEY‐VCH Verlag Wiley-VCH
Subjects:	Amino Acid Motifs Amino Acid Sequence Analytical, structural and metabolic biochemistry Biological and medical sciences Computational Biology Cross-affinity binding matrixes DNA Mutational Analysis Enzyme-Linked Immunosorbent Assay Fundamental and applied biological sciences. Psychology Glutathione Transferase - metabolism Humans Ligands Miscellaneous Molecular Sequence Data Peptides - chemistry Proline - chemistry Proline-rich peptides Protein Binding Protein domains Protein networks Protein Structure, Secondary Protein Structure, Tertiary Protein-to-protein interaction Proteins Signal Transduction Software Proteomics
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Summary:	WW domains are protein modules that bind proline‐rich ligands. WW domain‐ligand complexes are of importance as they have been implicated in several human diseases such as muscular dystrophy, cancer, hypertension, Alzheimer's, and Huntington's diseases. We report the results of a protein array aimed at mapping all the human WW domain protein‐protein interactions. Our biochemical approach integrates parallel synthesis of peptides, protein expression, and high‐throughput screening methodology combined with tools of bioinformatics. The results suggest that the majority of the bioinformatically predicted WW peptide ligands and most WW domains are functional, and that only about 10% of the measured domain‐ligand interactions are positive. The analysis of the WW domain protein arrays also underscores the importance of the amino acid residues surrounding the WW ligand core motifs for specific binding to WW domains. In addition, the methodology presented here allows for the rapid elucidation of WW domain‐ligand interactions with multiple applications including prediction of exact WW ligand binding sites, which can be applied to the mapping of other protein signaling domain families. Such information can be applied to the generation of protein interaction networks and identification of potential drug targets. To our knowledge, this report describes the first protein‐protein interaction map of a domain in the human proteome.
Bibliography:	ark:/67375/WNG-J7W9HXDW-4 ArticleID:PMIC200300632 istex:27A72AB29CFCD9D6B05A741FE452708A4F2E0F60 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	1615-9853 1615-9861
DOI:	10.1002/pmic.200300632