2LXH

NMR structure of the RING domain in ubiquitin ligase gp78

Summary for 2LXH

• Entry DOI: 10.2210/pdb2lxh/pdb
• NMR Information: BMRB: 18677
• Descriptor: E3 ubiquitin-protein ligase AMFR, ZINC ION (2 entities in total)
• Functional Keywords: ring domain, ubiquitin, ligase
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q9UKV5
• Total number of polymer chains: 1
• Total formula weight: 9372.27

Authors

Das, R.,Linag, Y.,Mariano, J.,Li, J.,Huang, T.,King, A.,Weissman, A.,Ji, X.,Byrd, R. (deposition date: 2012-08-27, release date: 2013-08-28, Last modification date: 2024-05-15)

Primary citation

Das, R.,Liang, Y.H.,Mariano, J.,Li, J.,Huang, T.,King, A.,Tarasov, S.G.,Weissman, A.M.,Ji, X.,Byrd, R.A.
Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine.
Embo J., 32:2504-2516, 2013

PubMed Abstract: RING finger proteins constitute the large majority of ubiquitin ligases (E3s) and function by interacting with ubiquitin-conjugating enzymes (E2s) charged with ubiquitin. How low-affinity RING-E2 interactions result in highly processive substrate ubiquitination is largely unknown. The RING E3, gp78, represents an excellent model to study this process. gp78 includes a high-affinity secondary binding region for its cognate E2, Ube2g2, the G2BR. The G2BR allosterically enhances RING:Ube2g2 binding and ubiquitination. Structural analysis of the RING:Ube2g2:G2BR complex reveals that a G2BR-induced conformational effect at the RING:Ube2g2 interface is necessary for enhanced binding of RING to Ube2g2 or Ube2g2 conjugated to Ub. This conformational effect and a key ternary interaction with conjugated ubiquitin are required for ubiquitin transfer. Moreover, RING:Ube2g2 binding induces a second allosteric effect, disrupting Ube2g2:G2BR contacts, decreasing affinity and facilitating E2 exchange. Thus, gp78 is a ubiquitination machine where multiple E2-binding sites coordinately facilitate processive ubiquitination.

PubMed: 23942235
DOI: 10.1038/emboj.2013.174

Experimental method

SOLUTION NMR