6GJZ

CryoEM structure of the MDA5-dsRNA filament in complex with AMPPNP

Summary for 6GJZ

• Entry DOI: 10.2210/pdb6gjz/pdb
• Related: 6G19 6G1S 6G1X
• EMDB information: 0012 4338 4340 4341
• Descriptor: Interferon-induced helicase C domain-containing protein 1, RNA (5'-R(P*CP*AP*AP*GP*CP*CP*GP*AP*GP*GP*AP*GP*AP*G)-3'), RNA (5'-R(P*CP*UP*CP*UP*CP*CP*UP*CP*GP*GP*CP*UP*UP*G)-3'), ... (5 entities in total)
• Functional Keywords: protein-rna complex, helical filament, atpase, innate immune receptor, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 123726.51

Authors

Yu, Q.,Qu, K.,Modis, Y. (deposition date: 2018-05-17, release date: 2018-11-21, Last modification date: 2024-05-15)

Primary citation

Yu, Q.,Qu, K.,Modis, Y.
Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis.
Mol. Cell, 72:999-1012.e6, 2018

PubMed Abstract: Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.

PubMed: 30449722
DOI: 10.1016/j.molcel.2018.10.012

Experimental method

ELECTRON MICROSCOPY (4.06 Å)