![]() Gerald Joyce and Bianca Lam for advice on in vitro transcription, Simon Hsu for assistance with DXMS, and Beam Lines 11-1 of SSRL, 19ID of APS, and 8.3.1 and 12.3.1 of ALS for crystallographic and SAXS data collection. Christopher Basler (Mount Sinai School of Medicine) for the gifts of Reston and Zaire VP35 cDNA, Marnie Fusco and Dafna Abelson for technical assistance, Drs. ![]() This work was supported by the Skaggs Institute for Chemical Biology a Career Award in the Biomedical Sciences and an Investigators in the Pathogenesis of Infectious Diseases Award from the Burroughs Wellcome Fund National Institutes of Health grants R21AI053423 (E.O.S.) and R01GM086701 (I.J.M.) as well as CA099835, CA118595, and AI076961 a Discovery Grant ( UC10591) from the University of California IUCRP Program and BiogenIDEC (V.L.W.), Training grants 5T32AI00760 and 2T32AI007244-26 to the TSRI Department of Immunology and Microbial Science (C.R.K. This work illustrates how ebolavirus VP35 could mask key recognition sites of molecules such as RIG-I, MDA-5, and Dicer to silence viral dsRNA in infection. Additional SAXS, DXMS, and dsRNA-binding experiments presented here support a model of cooperative dsRNA recognition in which binding of the first monomer assists binding of the next monomer of the oligomeric VP35 protein. ![]() The structures show that VP35 forms an unusual, asymmetric dimer on dsRNA binding, with each of the monomers binding dsRNA in a different way: one binds the backbone whereas the other caps the terminus. Here we present unbound and dsRNA-bound crystal structures of the dsRNA-binding domain of Reston ebolavirus VP35. Disease caused by ebolavirus is marked by early immunosuppression of innate immune signaling events, involving silencing and sequestration of double-stranded RNA (dsRNA) by the viral protein VP35. Ebolavirus causes a severe hemorrhagic fever and is divided into five distinct species, of which Reston ebolavirus is uniquely nonpathogenic to humans.
0 Comments
Leave a Reply. |