Structure of native c-Cbl; c-Cbl-ZAP-70 peptide complex; phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex; modified phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex and phosphoTyr371-c-Cbl-UbcH5B complex

Dou, H., Buetow, L., Hock, A., Sibbet, G., Vousden, K. and Huang, D. (2012) Structure of native c-Cbl; c-Cbl-ZAP-70 peptide complex; phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex; modified phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex and phosphoTyr371-c-Cbl-UbcH5B complex. [Data Collection]

Enlighten Publications URI: http://eprints.gla.ac.uk/id/eprint/61459

Collection description

To elucidate the mechanism of activation, we determined the structures of human CBL, a CBL-substrate peptide complex and a phosphorylated-Tyr371-CBL-E2-substrate peptide complex, and we compared them with the known structure of a CBL-E2-substrate peptide complex. Structural and biochemical analyses show that CBL adopts an autoinhibited RING conformation, where the RING's E2-binding surface associates with CBL to reduce E2 affinity. Tyr371 phosphorylation activates CBL by inducing LHR conformational changes that eliminate autoinhibition, flip the RING domain and E2 into proximity of the substrate-binding site and transform the RING domain into an enhanced E2-binding module. This activation is required for RTK ubiquitination. Our results present a mechanism for regulation of c-Cbl's activity by autoinhibition and phosphorylation-induced activation.

College / School: College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Date Deposited: 28 Mar 2019 12:40
URI: http://researchdata.gla.ac.uk/id/eprint/767

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Dou, H., Buetow, L., Hock, A., Sibbet, G., Vousden, K. and Huang, D. (2012); Structure of native c-Cbl; c-Cbl-ZAP-70 peptide complex; phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex; modified phosphoTyr371-c-Cbl-UbcH5B-ZAP-70 complex and phosphoTyr371-c-Cbl-UbcH5B complex

RCSB PDB

http://researchdata.gla.ac.uk/767

Retrieved: 2019-07-18