5G47

Structure of Gc glycoprotein from severe fever with thrombocytopenia syndrome virus in the trimeric postfusion conformation

Summary for 5G47

• Entry DOI: 10.2210/pdb5g47/pdb
• Descriptor: SFTSV GC, 2-acetamido-2-deoxy-beta-D-glucopyranose, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: viral protein, phlebovirus, viral membrane fusion, glycoprotein, class ii viral fusion, bunyavirus, huaiyangshan virus, emerging virus, zoonosis
• Biological source: SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME VIRUS (SFTSV)
• Total number of polymer chains: 3
• Total formula weight: 143862.69

Authors

Halldorsson, S.,Behrens, A.J.,Harlos, K.,Huiskonen, J.T.,Elliott, R.M.,Crispin, M.,Brennan, B.,Bowden, T.A. (deposition date: 2016-05-05, release date: 2016-07-06, Last modification date: 2024-10-09)

Primary citation

Halldorsson, S.,Behrens, A.,Harlos, K.,Huiskonen, J.T.,Elliott, R.M.,Crispin, M.,Brennan, B.,Bowden, T.A.
Structure of a Phleboviral Envelope Glycoprotein Reveals a Consolidated Model of Membrane Fusion.
Proc.Natl.Acad.Sci.USA, 113:7154-, 2016

PubMed 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.

PubMed: 27325770
DOI: 10.1073/PNAS.1603827113

Experimental method

X-RAY DIFFRACTION (2.45 Å)