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Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion

DOI: 10.1073/pnas.1603827113 DOI Help

Authors: Steinar Halldorsson (Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Diamond Light Source) , Anna-janina Behrens (Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford) , Karl Harlos (Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Diamond Light Source) , Juha T. Huiskonen (Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Diamond Light Source) , Richard M. Elliott (MRC–University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow) , Max Crispin (Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford) , Benjamin Brennan (MRC–University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow) , Thomas A. Bowden (Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 113 , PAGES 7154 - 7159

State: Published (Approved)
Published: June 2016
Diamond Proposal Number(s): 8423

Abstract: An emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (SFTSV) is responsible for thousands of clinical cases and associated fatalities in China, Japan, and South Korea. Akin to other phleboviruses, SFTSV relies on a viral glycoprotein, Gc, to catalyze the merger of endosomal host and viral membranes during cell entry. Here, we describe the postfusion structure of SFTSV Gc, revealing that the molecular transformations the phleboviral Gc undergoes upon host cell entry are conserved with otherwise unrelated alpha- and flaviviruses. By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever virus, we show that these changes involve refolding of the protein into a trimeric state. Reverse genetics and rescue of site-directed histidine mutants enabled localization of histidines likely to be important for triggering this pH-dependent process. These data provide structural and functional evidence that the mechanism of phlebovirus–host cell fusion is conserved among genetically and patho-physiologically distinct viral pathogens.

Journal Keywords: emerging virus; phlebovirus; viral membrane fusion; bunyavirus; structure

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography