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WT MDA5-dsRNA filaments in complex with ADP

ABSTRACT:

SUBMITTER: Yorgo Modis

PROVIDER: EMPIAR-10653 | biostudies-other |

REPOSITORIES: biostudies-other

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MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA.

Yu Qin Q Herrero Del Valle Alba A Singh Rahul R Modis Yorgo Y

Nature communications 20211118 1

Our innate immune responses to viral RNA are vital defenses. Long cytosolic double-stranded RNA (dsRNA) is recognized by MDA5. The ATPase activity of MDA5 contributes to its dsRNA binding selectivity. Mutations that reduce RNA selectivity can cause autoinflammatory disease. Here, we show how the disease-associated MDA5 variant M854K perturbs MDA5-dsRNA recognition. M854K MDA5 constitutively activates interferon signaling in the absence of exogenous RNA. M854K MDA5 lacks ATPase activity and binds ...[more]

PMID: 34795277

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