PDBsum entry 4nqk

Hydrolase/apoptosis

PDB id: 4nqk

Contents

Protein chains

188 a.a.

(+ 0 more) 72 a.a.

PDB id:

4nqk

Name:

Hydrolase/apoptosis

Title:

Structure of an ubiquitin complex

Structure:

Probable atp-dependent RNA helicase ddx58. Chain: a, b, c, d. Fragment: n-terminal tandem card domain, unp residues 1-200. Synonym: dead box protein 58, rig-i-like receptor 1, rlr-1, retinoic acid-inducible gene 1 protein, rig-1, retinoic acid-inducible gene i protein, rig-i. Engineered: yes. Ubiquitin. Chain: e, f, g, h, i, j.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ddx58. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ubc. Expression_system_taxid: 562

Resolution:

3.70Å R-factor: 0.225 R-free: 0.285

Authors:

A.Peisley,B.Wu,S.Hur

Key ref:

A.Peisley et al. (2014). Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature, 509, 110-114. PubMed id: 24590070 DOI: 10.1038/nature13140

Date:

25-Nov-13 Release date: 05-Mar-14

Protein chains

O95786  (DDX58_HUMAN) -  Antiviral innate immune response receptor RIG-I from Homo sapiens

Seq: 925 a.a.

Struc: 188 a.a.

Protein chains

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 72 a.a.

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 3: Chains E, F, G, H, I, J: E.C.?

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.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nature13140

Nature 509:110-114 (2014)

PubMed id: 24590070

Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I.

A.Peisley, B.Wu, H.Xu, Z.J.Chen, S.Hur.

ABSTRACT

Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of non-covalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ubn) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream signal activation. Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.