PDBsum entry 5fer

Ligase

PDB id: 5fer

Contents

Protein chains

79 a.a.

145 a.a.

76 a.a.

Metals

_ZN ×4

Waters ×68

PDB id:

5fer

Name:

Ligase

Title:

Complex of trim25 ring with ubch5-ub

Structure:

E3 ubiquitin/isg15 ligase trim25. Chain: a, d. Synonym: estrogen-responsive finger protein,ring finger protein 147, ring-type e3 ubiquitin transferase,tripartite motif-containing protein 25,ubiquitin/isg15-conjugating enzyme trim25,zinc finger protein 147. Engineered: yes. Ubiquitin-conjugating enzyme e2 d1. Chain: b, e.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: trim25, efp, rnf147, znf147. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ube2d1, sft, ubc5a, ubch5, ubch5a. Bos taurus. Bovine.

Resolution:

2.34Å R-factor: 0.229 R-free: 0.273

Authors:

K.Rittinger,M.G.Koliopoulos,D.Esposito

Key ref:

M.G.Koliopoulos et al. (2016). Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity. Embo J, 35, 1204-1218. PubMed id: 27154206 DOI: 10.15252/embj.201593741

Date:

17-Dec-15 Release date: 18-May-16

Protein chains

Q14258  (TRI25_HUMAN) -  E3 ubiquitin/ISG15 ligase TRIM25 from Homo sapiens

Seq: 630 a.a.

Struc: 79 a.a.

Protein chains

P51668  (UB2D1_HUMAN) -  Ubiquitin-conjugating enzyme E2 D1 from Homo sapiens

Seq: 147 a.a.

Struc: 145 a.a.*

Protein chains

P62992  (RS27A_BOVIN) -  Ubiquitin-ribosomal protein eS31 fusion protein from Bos taurus

Seq: 156 a.a.

Struc: 76 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, D: 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
• Enzyme class 3: Chains A, D: E.C.6.3.2.n3 - ?????
• Enzyme class 4: Chains B, E: 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 5: Chains B, E: E.C.2.3.2.24 - (E3-independent) E2 ubiquitin-conjugating enzyme.
• Reaction: S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N₆- monoubiquitinyl-[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: 10.15252/embj.201593741

Embo J 35:1204-1218 (2016)

PubMed id: 27154206

Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity.

M.G.Koliopoulos, D.Esposito, E.Christodoulou, I.A.Taylor, K.Rittinger.

ABSTRACT

TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function.