Title | Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Ceregido Pérez, M de los Á., A. Garcia-Pino, J. L. Ortega-Roldan, S. Casares, O. López Mayorga, J. Bravo, N. A. J. van Nuland, and A. I. Azuaga |
Journal | FEBS J |
Volume | 280 |
Issue | 14 |
Pagination | 3399-415 |
Date Published | 2013 Jul |
ISSN | 1742-4658 |
Keywords | Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antigens, CD2, Cytoskeletal Proteins, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Proline, Protein Binding, Protein Structure, Secondary, Proto-Oncogene Proteins c-cbl, Scattering, Small Angle, src Homology Domains, Thermodynamics, Titrimetry, X-Ray Diffraction |
Abstract | The CD2AP (CD2-associated protein) and CIN85 (Cbl-interacting protein of 85 kDa) adaptor proteins each employ three Src homology 3 (SH3) domains to cluster protein partners and ensure efficient signal transduction and down-regulation of tyrosine kinase receptors. Using NMR, isothermal titration calorimetry and small-angle X-ray scattering methods, we have characterized several binding modes of the N-terminal SH3 domain (SH3A) of CD2AP and CIN85 with two natural atypical proline-rich regions in CD2 (cluster of differentiation 2) and Cbl-b (Casitas B-lineage lymphoma), and compared these data with previous studies and published crystal structures. Our experiments show that the CD2AP-SH3A domain forms a type II dimer with CD2 and both type I and type II dimeric complexes with Cbl-b. Like CD2AP, the CIN85-SH3A domain forms a type II complex with CD2, but a trimeric complex with Cbl-b, whereby the type I and II interactions take place at the same time. Together, these results explain how multiple interactions among similar SH3 domains and ligands produce a high degree of diversity in tyrosine kinase, cell adhesion or T-cell signaling pathways. |
DOI | 10.1111/febs.12333 |
Alternate Journal | FEBS J. |
PubMed ID | 23663663 |
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