5JC7

Crystal structure of chicken MDA5 with 5'p 24-mer dsRNA and ADP-Mg2+ at 2.75 A resolution.

Summary for 5JC7

• Entry DOI: 10.2210/pdb5jc7/pdb
• Descriptor: Melanoma differentiation associated protein-5, RNA (5'-R(P*GP*GP*AP*CP*GP*UP*CP*AP*UP*GP*CP*GP*CP*AP*UP*GP*AP*CP*GP*UP*CP*CP*CP*C)-3'), RNA (5'-R(P*GP*GP*GP*AP*CP*GP*UP*CP*AP*UP*GP*CP*GP*CP*AP*UP*GP*AP*CP*GP*UP*CP*CP*C)-3'), ... (6 entities in total)
• Functional Keywords: innate immune pattern recognition receptor, rig-i like helicase, dsrna dependent atpase, zinc-containing ctd domain, immune system
• Biological source: Gallus gallus (Chicken); More
• Total number of polymer chains: 4
• Total formula weight: 180072.29

Authors

Cusack, S.,Uchikawa, E. (deposition date: 2016-04-14, release date: 2016-06-01, Last modification date: 2024-01-10)

Primary citation

Uchikawa, E.,Lethier, M.,Malet, H.,Brunel, J.,Gerlier, D.,Cusack, S.
Structural Analysis of dsRNA Binding to Anti-viral Pattern Recognition Receptors LGP2 and MDA5.
Mol.Cell, 62:586-602, 2016

PubMed 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.

PubMed: 27203181
DOI: 10.1016/j.molcel.2016.04.021

Experimental method

X-RAY DIFFRACTION (2.75 Å)