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Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*

Ceregido, M. Angeles, Garcia-Pino, Abel, Ortega-Roldan, Jose L., Casares, Salvador, López Mayorga, Obdulio, Bravo, Jeronimo, van Nuland, Nico A. J., Azuaga, Ana I. (2013) Multimeric and differential binding of CIN85/CD2AP with two atypical proline-rich sequences from CD2 and Cbl-b*. FEBS Journal, 280 (14). pp. 3399-3415. ISSN 1742-464X. E-ISSN 1742-4658. (doi:10.1111/febs.12333) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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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.

Item Type: Article
DOI/Identification number: 10.1111/febs.12333
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Jose Ortega-Roldan
Date Deposited: 31 Jul 2017 14:08 UTC
Last Modified: 29 May 2019 19:16 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62499 (The current URI for this page, for reference purposes)
Ortega-Roldan, Jose L.: https://orcid.org/0000-0002-6316-4390
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