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. 2003 Nov;43(1-3):105–111. doi: 10.1023/B:CYTO.0000039913.56708.06

Probing WW Domains to Uncover and Refine Determinants of Specificity in Ligand Recognition

X Espanel 1, N Navin 2, Y Kato 3, M Tanokura 3, M Sudol 1
PMCID: PMC3449593  PMID: 19003214

Abstract

Understanding the specificity of protein-protein interaction mediated by domains and their ligands will have strong impact on basic and applied research. Visual inspection of WW domain sequences prompted a general classification of the domains into two large subfamilies. One subfamily contains two consecutive aromatic residues in the beta 2 strand of the domain whereas the other contains three or four consecutive aromatic residues in the same position. In the recent past, we proposed a rule of ‘two vs. three aromatics’ in the beta 2 strand of WW domains as a molecular discriminator between Class I and Class II WW domains, which recognize PPxY or PPLP motifs, respectively. Using phage display libraries expressing WW domains with random sequences replacing a part of the beta 2 strand, we provided additional evidence supporting our rule. We conclude that three consecutive aromatic amino acids within the beta 2 strand of WW domain are required but not always sufficient for the WW domain to belong to Class II.

Keywords: binding specificity, domains, protein modules, protein-protein recognition

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