title: Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation.
abstract: Hantaviruses are important emerging human pathogens and are the causative agents of serious diseases in humans with high mortality rates. Like other members in the Bunyaviridae family their M segment encodes two glycoproteins, GN and GC, which are responsible for the early events of infection. Hantaviruses deliver their tripartite genome into the cytoplasm by fusion of the viral and endosomal membranes in response to the reduced pH of the endosome. Unlike phleboviruses (e.g. Rift valley fever virus), that have an icosahedral glycoprotein envelope, hantaviruses display a pleomorphic virion morphology as GN and GC assemble into spikes with apparent four-fold symmetry organized in a grid-like pattern on the viral membrane. Here we present the crystal structure of glycoprotein C (GC) from Puumala virus (PUUV), a representative member of the Hantavirus genus. The crystal structure shows GC as the membrane fusion effector of PUUV and it presents a class II membrane fusion protein fold. Furthermore, GC was crystallized in its post-fusion trimeric conformation that until now had been observed only in Flavi- and Togaviridae family members. The PUUV GC structure together with our functional data provides intriguing evolutionary and mechanistic insights into class II membrane fusion proteins and reveals new targets for membrane fusion inhibitors against these important pathogens.
authors: The Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
authors: Shmuel
authors: S
authors: Willensky
authors: The Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
authors: Hagit
authors: http://orcid.org/0000-0003-4455-5166
authors: H
authors: Bar-Rogovsky
authors: Molecular Virology Laboratory, Fundación Ciencia & Vida, Santiago, Chile.
authors: Eduardo A
authors: EA
authors: Bignon
authors: Molecular Virology Laboratory, Fundación Ciencia & Vida, Santiago, Chile.
authors: Nicole D
authors: ND
authors: Tischler
authors: Dept. of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors: Yorgo
authors: http://orcid.org/0000-0002-6084-0429
authors: Y
authors: Modis
authors: The Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
authors: Moshe
authors: M
authors: Dessau
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D011487:Protein Conformation; D029262:Puumala virus / Q000737:chemistry*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry*
chemical_list: D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1