4LAD

Crystal Structure of the Ube2g2:RING-G2BR complex

Summary for 4LAD

• Entry DOI: 10.2210/pdb4lad/pdb
• Related: 2LXH 2LXP
• Descriptor: Ubiquitin-conjugating enzyme E2 G2, E3 ubiquitin-protein ligase AMFR, ZINC ION, ... (5 entities in total)
• Functional Keywords: e2:e3 complex, ligase-ligase complex, ligase/ligase
• Biological source: Homo sapiens (human); More
• Cellular location: Endoplasmic reticulum membrane ; Multi-pass membrane protein : Q9UKV5
• Total number of polymer chains: 2
• Total formula weight: 34360.18

Authors

Liang, Y.-H.,Li, J.,Das, R.,Byrd, R.A.,Ji, X. (deposition date: 2013-06-19, release date: 2013-08-28, Last modification date: 2023-09-20)

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

X-RAY DIFFRACTION (2.3 Å)