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

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


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.

• Content Type Journal Article
• Pages 1-15
• DOI 10.1007/s10858-011-9505-5
• Authors
  • Jose L. Ortega Roldan, Departamento de QuÃ*mica FÃ*sica e Instituto de BiotecnologÃ*a, Facultad de Ciencias, Universidad de Granada, Fuentenueva s/n, 18071 Granada, Spain
  • Martin Blackledge, Protein Dynamics and Flexibility by NMR, Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, 41 Rue Jules Horowitz, Grenoble, 38027 France
  • Nico A. J. van Nuland, Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium
  • Ana I. Azuaga, Departamento de QuÃ*mica FÃ*sica e Instituto de BiotecnologÃ*a, Facultad de Ciencias, Universidad de Granada, Fuentenueva s/n, 18071 Granada, Spain

• • Journal Journal of Biomolecular NMR
  • Online ISSN 1573-5001
  • Print ISSN 0925-2738

Source: Journal of Biomolecular NMR