5J3X

Structure of c-CBL Y371F

Summary for 5J3X

• Entry DOI: 10.2210/pdb5j3x/pdb
• Descriptor: E3 ubiquitin-protein ligase CBL, ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ubiquitin ligase, ring e3, ligase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P22681
• Total number of polymer chains: 6
• Total formula weight: 271366.32

Authors

Huang, D.T.,Buetow, L.,Dou, H. (deposition date: 2016-03-31, release date: 2016-09-21, Last modification date: 2024-01-10)

Primary citation

Buetow, L.,Tria, G.,Ahmed, S.F.,Hock, A.,Dou, H.,Sibbet, G.J.,Svergun, D.I.,Huang, D.T.
Casitas B-lineage lymphoma linker helix mutations found in myeloproliferative neoplasms affect conformation.
Bmc Biol., 14:76-76, 2016

PubMed Abstract: Casitas B-lineage lymphoma (Cbl or c-Cbl) is a RING ubiquitin ligase that negatively regulates protein tyrosine kinase (PTK) signalling. Phosphorylation of a conserved residue (Tyr371) on the linker helix region (LHR) between the substrate-binding and RING domains is required to ubiquitinate PTKs, thereby flagging them for degradation. This conserved Tyr is a mutational hotspot in myeloproliferative neoplasms. Previous studies have revealed that select point mutations in Tyr371 can potentiate transformation in cells and mice but not all possible mutations do so. To trigger oncogenic potential, Cbl Tyr371 mutants must perturb the LHR-substrate-binding domain interaction and eliminate PTK ubiquitination. Although structures of native and pTyr371-Cbl are available, they do not reveal how Tyr371 mutations affect Cbl's conformation. Here, we investigate how Tyr371 mutations affect Cbl's conformation in solution and how this relates to Cbl's ability to potentiate transformation in cells.

PubMed: 27609087
DOI: 10.1186/s12915-016-0298-6

Experimental method

X-RAY DIFFRACTION (2.822 Å)