| Structural highlights
Function
UB2G2_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Involved in endoplasmic reticulum-associated degradation (ERAD).[1] [2]
Publication Abstract from PubMed
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.
Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine.,Das R, Liang YH, Mariano J, Li J, Huang T, King A, Tarasov SG, Weissman AM, Ji X, Byrd RA EMBO J. 2013 Aug 13. doi: 10.1038/emboj.2013.174. PMID:23942235[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ Sato T, Sako Y, Sho M, Momohara M, Suico MA, Shuto T, Nishitoh H, Okiyoneda T, Kokame K, Kaneko M, Taura M, Miyata M, Chosa K, Koga T, Morino-Koga S, Wada I, Kai H. STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. Mol Cell. 2012 Jul 13;47(1):99-110. doi: 10.1016/j.molcel.2012.04.015. Epub 2012 , May 17. PMID:22607976 doi:10.1016/j.molcel.2012.04.015
- ↑ Das R, Liang YH, Mariano J, Li J, Huang T, King A, Tarasov SG, Weissman AM, Ji X, Byrd RA. Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine. EMBO J. 2013 Aug 13. doi: 10.1038/emboj.2013.174. PMID:23942235 doi:10.1038/emboj.2013.174
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