PDBsum entry 2lxp

Ligase

PDB id: 2lxp

Contents

Protein chains

156 a.a.

27 a.a.

58 a.a.

Metals

_ZN ×2

PDB id:

2lxp

Name:

Ligase

Title:

Nmr structure of two domains in ubiquitin ligase gp78, ring and g2br, bound to its conjugating enzyme ube2g

Structure:

Ubiquitin-conjugating enzyme e2 g2. Chain: a. Fragment: unp residues 2-165. Synonym: ubiquitin carrier protein g2, ubiquitin-protein ligase g2. Engineered: yes. E3 ubiquitin-protein ligase amfr. Chain: b. Fragment: unp residues 574-600. Synonym: autocrine motility factor receptor, isoform 2, amf receptor,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ube2g2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: amfr, rnf45.

NMR struc:

20 models

Authors:

R.Das,Y.Linag,J.Mariano,J.Li,T.Huang,A.King,A.Weissman,X.Ji,R.Byrd

Key ref:

R.Das et al. (2013). Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine. Embo J, 32, 2504-2516. PubMed id: 23942235 DOI: 10.1038/emboj.2013.174

Date:

30-Aug-12 Release date: 28-Aug-13

Protein chain

P60604  (UB2G2_HUMAN) -  Ubiquitin-conjugating enzyme E2 G2 from Homo sapiens

Seq: 165 a.a.

Struc: 156 a.a.

Protein chain

Q9UKV5  (AMFR_HUMAN) -  E3 ubiquitin-protein ligase AMFR from Homo sapiens

Seq: 643 a.a.

Struc: 27 a.a.

Protein chain

Q9UKV5  (AMFR_HUMAN) -  E3 ubiquitin-protein ligase AMFR from Homo sapiens

Seq: 643 a.a.

Struc: 58 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.2.3.2.23 - E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L- cysteine
• Enzyme class 3: Chains B, C: E.C.2.3.2.36 - RING-type E3 ubiquitin transferase (cysteine targeting).
• Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1038/emboj.2013.174

Embo J 32:2504-2516 (2013)

PubMed id: 23942235

Allosteric regulation of E2:E3 interactions promote a processive ubiquitination machine.

R.Das, Y.H.Liang, J.Mariano, J.Li, T.Huang, A.King, S.G.Tarasov, A.M.Weissman, X.Ji, R.A.Byrd.

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.