Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition

• DOI: 10.1073/pnas.1113651108
• Publication Date: 2011-12-13T05:15:49Z
• Authors: Alys Peisley; Cecilie Lin; Bin Wu; McGhee Orme-Johnson; Mengyuan Liu; Thomas Walz; Sun Hur
• Keywords: MDA5; RNA Silencing

MDA5, an RIG-I-like helicase, is a conserved cytoplasmic viral RNA sensor, which recognizes dsRNA from wide-range of viruses in length-dependent manner. It has been proposed that MDA5 forms higher-order structures upon recognition or during antiviral signaling, however the organization and nature this oligomeric state unknown. We report here cooperatively assembles into filamentous oligomer composed repeating segmental arrangement dimers along length dsRNA. Binding to stimulates its ATP hydrolysis activity with little coordination between neighboring molecules within filament. Individual turn renders intrinsic kinetic instability filament, triggering dissociation at rate inversely proportional filament length. These results suggest previously unrecognized role control assembly disassembly processes, thereby autoregulating interaction dsRNA, provides potential basis for signaling.