Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP.

TitleSolution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP.
Publication TypeJournal Article
Year of Publication2011
AuthorsRoldan, J. L. Ortega, M. Blackledge, N. A. J. van Nuland, and A. I. Azuaga
JournalJ Biomol NMR
Volume50
Issue2
Pagination103-17
Date Published2011 Jun
ISSN1573-5001
KeywordsAdaptor Proteins, Signal Transducing, Amino Acid Sequence, Cytoskeletal Proteins, Deuterium Exchange Measurement, Models, Molecular, Molecular Dynamics Simulation, Molecular Sequence Data, Protein Conformation, Protein Stability, Recombinant Proteins, Sequence Alignment, Solutions, src Homology Domains, Thermodynamics
Abstract

CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. It contains three N-terminal SH3 domains that are able to interact among others with CD2, ALIX, c-Cbl and Ubiquitin. To understand the role of the individual SH3 domains of this adaptor protein we have performed a complete structural, thermodynamic and dynamic characterization of the separate domains using NMR and DSC. The energetic contributions to the stability and the backbone dynamics have been related to the structural features of each domain using the structure-based FoldX algorithm. We have found that the N-terminal SH3 domain of both adaptor proteins CD2AP and CIN85 are the most stable SH3 domains that have been studied until now. This high stability is driven by a more extensive network of intra-molecular interactions. We believe that this increased stabilization of N-terminal SH3 domains in adaptor proteins is crucial to maintain the necessary conformation to establish the proper interactions critical for the recruitment of their natural targets.

DOI10.1007/s10858-011-9505-5
Alternate JournalJ. Biomol. NMR
PubMed ID21519904