PDBsum entry 5jc3

Immune system

PDB id: 5jc3

Contents

Protein chains

668 a.a.

DNA/RNA

Ligands

ADP ×2

Metals

_ZN ×2

_MG ×2

PDB id:

5jc3

Name:

Immune system

Title:

Crystal structure of chicken mda5 with 5'p 10-mer dsrna and adp-mg2+ at 2.6 a resolution (monoclinic form, twinned).

Structure:

Melanoma differentiation associated protein-5. Chain: a, b. Engineered: yes. Mutation: yes. RNA (5'-r(p Gp Gp Up Ap Cp Gp Up Ap Cp C)-3'). Chain: x, y, c, d. Engineered: yes. Mutation: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Gene: mda5. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.60Å R-factor: 0.272 R-free: 0.290

Authors:

S.Cusack,E.Uchikawa

Key ref:

E.Uchikawa et al. (2016). Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5. Mol Cell, 62, 586-602. PubMed id: 27203181 DOI: 10.1016/j.molcel.2016.04.021

Date:

14-Apr-16 Release date: 01-Jun-16

Protein chains

D9N195  (D9N195_CHICK) -  RNA helicase from Gallus gallus

Seq: 1001 a.a.

Struc: 668 a.a.*

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

DNA/RNA chains

G-G-U-A-C-G-U-A-C-C 10 bases

G-G-U-A-C-G-U-A-C-C 10 bases

G-G-U-A-C-G-U-A-C-C 10 bases

G-G-U-A-C-G-U-A-C-C 10 bases

Enzyme reactions

• Enzyme class: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + phosphate + H(+)

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

reference

DOI no: 10.1016/j.molcel.2016.04.021

Mol Cell 62:586-602 (2016)

PubMed id: 27203181

Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5.

E.Uchikawa, M.Lethier, H.Malet, J.Brunel, D.Gerlier, S.Cusack.

ABSTRACT

RIG-I and MDA5 sense virus-derived short 5'ppp blunt-ended or long dsRNA, respectively, causing interferon production. Non-signaling LGP2 appears to positively and negatively regulate MDA5 and RIG-I signaling, respectively. Co-crystal structures of chicken (ch) LGP2 with dsRNA display a fully or semi-closed conformation depending on the presence or absence of nucleotide. LGP2 caps blunt, 3' or 5' overhang dsRNA ends with 1 bp longer overall footprint than RIG-I. Structures of 1:1 and 2:1 complexes of chMDA5 with short dsRNA reveal head-to-head packing rather than the polar head-to-tail orientation described for long filaments. chLGP2 and chMDA5 make filaments with a similar axial repeat, although less co-operatively for chLGP2. Overall, LGP2 resembles a chimera combining a MDA5-like helicase domain and RIG-I like CTD supporting both stem and end binding. Functionally, RNA binding is required for LGP2-mediated enhancement of MDA5 activation. We propose that LGP2 end-binding may promote nucleation of MDA5 oligomerization on dsRNA.