@misc{10481/99161,
year = {2012},
month = {3},
url = {https://hdl.handle.net/10481/99161},
abstract = {In spite of its biomedical relevance, polyproline recognition is still not fully understood.
The disagreement between the current description of SH3 complexes and their thermodynamic
behavior calls for a revision of the SH3 binding paradigm. Recently, Abl-SH3 was
demonstrated to recognize its ligands by a dual binding mechanism involving a robust network
of water-mediated hydrogen bonds that complements the canonical hydrophobic interactions.
The systematic analysis of the SH3 structural database presented here reveals that this dual
binding mode is universal to SH3 domains. Tightly bound, buried interfacial water molecules
were found in all SH3 complexes studied mediating the interaction between the peptide ligand
and the domain. Moreover, structural waters were also identified in a high percentage of free
SH3 domains. A detailed analysis of the pattern of water-mediated interactions enabled the
identification of conserved hydration sites in the polyproline-recognition region and the
establishment of relationships between hydration profiles and the sequence of both, ligands and
SH3 domains. Water-mediated interactions were also systematically observed in WW, UEV and
EVH-1 structures. These results clearly indicate that the current description of proline-rich
sequence recognition by protein-protein interaction modules is incomplete and insufficient for a
correct understanding of these systems. A new binding paradigm is required that includes
interfacial water molecules as relevant elements in polyproline recognition.},
organization = {This work was supported by Grants BIO2006-15517-CO2-01 and BIO2009-13261-
CO2-01 from the Spanish Ministry of Science and Technology, FEDER Funds and grant CVI-
5915 from the Andalusian Government. J.M. Martin-Garcia was supported by a predoctoral
research contract from the Spanish Ministry of Science and Technology},
publisher = {Portland Press Ltd.},
keywords = {Binding energetics},
keywords = {Proline-rich ligand recognition},
keywords = {Protein-protein interaction module},
keywords = {SH3 domain},
keywords = {Water-mediated interaction},
title = {Interfacial water molecules in SH3 interactions: a revised paradigm for polyproline recognition},
doi = {10.1042/BJ20111089},
author = {Martín-García, José Manuel and Ruiz Sanz, Javier and Luque Fernández, Irene},
}