Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation
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Authors
Willensky, Shmuel
Bar-Rogovsky, Hagit
Bignon, Eduardo A
Tischler, Nicole D
Dessau, Moshe
Publication Date
2016-10-26Journal Title
PLOS Pathogens
Volume
12
Number
e1005948
Language
English
Type
Article
This Version
VoR
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Willensky, S., Bar-Rogovsky, H., Bignon, E. A., Tischler, N. D., Modis, Y. E., & Dessau, M. (2016). Crystal Structure of Glycoprotein C from a Hantavirus in the Post-fusion Conformation. PLOS Pathogens, 12 (e1005948)https://doi.org/10.1371/journal.ppat.1005948
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.
Sponsorship
Wellcome Trust (101908/Z/13/Z)
Identifiers
External DOI: https://doi.org/10.1371/journal.ppat.1005948
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266459
Rights
Attribution 4.0 International