PDBsum entry 4tkp

Ligase

PDB id: 4tkp

Contents

Protein chains

145 a.a.

63 a.a.

Ligands

SO4

Metals

_ZN ×2

Waters ×49

PDB id:

4tkp

Name:

Ligase

Title:

Complex of ubc13 with the ring domain of the trim5alpha retroviral restriction factor

Structure:

Ubiquitin-conjugating enzyme e2 n. Chain: a. Synonym: bendless-like ubiquitin-conjugating enzyme,ubc13,ubch13, ubiquitin carrier protein n,ubiquitin-protein ligase n. Engineered: yes. Tripartite motif-containing protein 5. Chain: b. Fragment: unp residues 2-92. Synonym: trim5alpha.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ube2n, blu. Expressed in: escherichia coli. Expression_system_taxid: 511693. Macaca mulatta. Rhesus macaque. Organism_taxid: 9544.

Resolution:

2.08Å R-factor: 0.226 R-free: 0.255

Authors:

R.Johnson,A.B.Taylor,P.J.Hart,D.N.Ivanov

Key ref:

Z.Yudina et al. (2015). RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin. Cell Rep, 12, 788-797. PubMed id: 26212332 DOI: 10.1016/j.celrep.2015.06.072

Date:

27-May-14 Release date: 22-Jul-15

Protein chain

P61088  (UBE2N_HUMAN) -  Ubiquitin-conjugating enzyme E2 N from Homo sapiens

Seq: 152 a.a.

Struc: 145 a.a.

Protein chain

Q0PF16  (TRIM5_MACMU) -  Tripartite motif-containing protein 5 from Macaca mulatta

Seq: 497 a.a.

Struc: 63 a.a.

Enzyme reactions

• Enzyme class 1: 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 2: Chain B: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

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: 10.1016/j.celrep.2015.06.072

Cell Rep 12:788-797 (2015)

PubMed id: 26212332

RING Dimerization Links Higher-Order Assembly of TRIM5α to Synthesis of K63-Linked Polyubiquitin.

Z.Yudina, A.Roa, R.Johnson, N.Biris, D.A.de Souza Aranha Vieira, V.Tsiperson, N.Reszka, A.B.Taylor, P.J.Hart, B.Demeler, F.Diaz-Griffero, D.N.Ivanov.

ABSTRACT

Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub) ligases promote innate immune responses by catalyzing synthesis of polyubiquitin chains linked through lysine 63 (K63). Here, we investigate the mechanism by which the TRIM5α retroviral restriction factor activates Ubc13, the K63-linkage-specific E2. Structural, biochemical, and functional characterization of the TRIM5α:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub conjugate requires dimerization of the TRIM5α RING domain. Our data explain how higher-order oligomerization of TRIM5α, which is promoted by the interaction with the retroviral capsid, enhances the E3 Ub ligase activity of TRIM5α and contributes to its antiretroviral function. This E3 mechanism, in which RING dimerization is transient and depends on the interaction of the TRIM protein with the ligand, is likely to be conserved in many members of the TRIM family and may have evolved to facilitate recognition of repetitive epitope patterns associated with infection.