2K4D

E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity

Summary for 2K4D

• Entry DOI: 10.2210/pdb2k4d/pdb
• Related: 1FBV
• NMR Information: BMRB: 15796
• Descriptor: E3 ubiquitin-protein ligase CBL, ZINC ION (2 entities in total)
• Functional Keywords: protein, ubiquitin, c-cbl, ubch5b, ubch7, calcium, cytoplasm, ligase, metal-binding, phosphoprotein, proto-oncogene, sh2 domain, ubl conjugation pathway, zinc, zinc-finger
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 9518.48

Authors

Huang, A.,De Jong, R.N.,Wienk, H.,Winkler, S.G.,Timmers, H.T.M.,Boelens, R. (deposition date: 2008-06-06, release date: 2009-01-20, Last modification date: 2024-10-30)

Primary citation

Huang, A.,de Jong, R.N.,Wienk, H.,Winkler, G.S.,Timmers, H.T.M.,Boelens, R.
E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity
J.Mol.Biol., 385:507-519, 2009

PubMed Abstract: The E2 ubiquitin-conjugating enzymes UbcH7 and UbcH5B both show specific binding to the RING (really interesting new gene) domain of the E3 ubiquitin-protein ligase c-Cbl, but UbcH7 hardly supports ubiquitination of c-Cbl and substrate in a reconstituted system. Here, we found that neither structural changes nor subtle differences in the E2-E3 interaction surface are possible explanations for the functional specificity of UbcH5B and UbcH7 in their interaction with c-Cbl. The quick transfer of ubiquitin from the UbcH5B-Ub thioester to c-Cbl or other ubiquitin acceptors suggests that UbcH5B might functionally be a relatively pliable E2 enzyme. In contrast, the UbcH7-Ub thioester is too stable to transfer ubiquitin under our assay conditions, indicating that UbcH7 might be a more specific E2 enzyme. Our results imply that the interaction specificity between c-Cbl and E2 is required but not sufficient for transfer of ubiquitin to potential targets.

PubMed: 18996392
DOI: 10.1016/j.jmb.2008.10.044

Experimental method

SOLUTION NMR