PDBsum entry 2lvp

Signaling protein/ligase

PDB id: 2lvp

Contents

Protein chains

76 a.a.

52 a.a.

PDB id:

2lvp

Name:

Signaling protein/ligase

Title:

Gp78cue domain bound to the distal ubiquitin of k48-linked diubiquitin

Structure:

Ubiquitin. Chain: a, b. Engineered: yes. E3 ubiquitin-protein ligase amfr. Chain: c. Fragment: cue domain residues 453-504. Synonym: autocrine motility factor receptor, isoform 2, amf receptor, isoform 2, ring finger protein 45, gp78. Engineered: yes

Source:

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

NMR struc:

20 models

Authors:

S.Liu,Y.Chen,T.Huang,S.G.Tarasov,A.King,J.Li,A.M.Weissman,R.A.Byrd, R.Das

Key ref:

S.Liu et al. (2012). Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains. Structure, 20, 2138-2150. PubMed id: 23123110

Date:

09-Jul-12 Release date: 21-Nov-12

Protein chains

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 76 a.a.

Protein chain

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

Seq: 643 a.a.

Struc: 52 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B: E.C.?
• Enzyme class 3: Chain 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.

Structure 20:2138-2150 (2012)

PubMed id: 23123110

Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains.

S.Liu, Y.Chen, J.Li, T.Huang, S.Tarasov, A.King, A.M.Weissman, R.A.Byrd, R.Das.

ABSTRACT

Recognition of ubiquitin and polyubiquitin chains by ubiquitin-binding domains (UBDs) is vital for ubiquitin-mediated signaling pathways. The endoplasmic reticulum resident RING finger ubiquitin ligase (E3) gp78 regulates critical proteins via the ubiquitin-proteasome system to maintain cellular homeostasis and includes a UBD known as the CUE domain, which is essential for function. A probable role of this domain is to recognize ubiquitin-modified substrates, enabling gp78 to assemble polyubiquitin chains on these substrates and mark them for degradation. Here, we report the molecular details of the interaction of gp78CUE domain with ubiquitin and diubiquitin. The gp78CUE domain exhibits a well-defined set of interactions with ubiquitin and a dynamic, promiscuous interaction with diubiquitin chains. This leads to a model in which the CUE domain functions to both facilitate substrate binding and enable switching between adjacent ubiquitin molecules of a growing chain to enable processivity in ubiquitination.