Crystal structure of glycoprotein C from Rift Valley fever virus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 5; pp. 1696 - 1701
• Main Authors: Dessau, Moshe, Modis, Yorgo
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29.01.2013; National Acad Sciences
• Subjects: Alphaviruses; Amino Acids - chemistry; animal pathogens; Animals; Biological Sciences; Cell membranes; Cells; Crystal structure; Crystallography, X-Ray; cytoplasm; Dimers; Evolution; Flaviviridae; Flavivirus; genome; Glycoproteins; humans; Hydrogen Bonding; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; lipids; membrane fusion; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membranes; Models, Molecular; Molecular structure; Orthobunyavirus; Protein Conformation; Protein Multimerization; Protein Structure, Tertiary; Proteins; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Rift Valley fever phlebovirus; Rift Valley fever virus; Rift Valley fever virus - genetics; Rift Valley fever virus - metabolism; Sf9 Cells; Vector-borne diseases; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Viruses
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1217780110

Rift Valley fever virus (RVFV), like many other Bunyaviridae family members, is an emerging human and animal pathogen. Bunyaviruses have an outer lipid envelope bearing two glycoproteins, G N and G C, required for cell entry. Bunyaviruses deliver their genome into the host-cell cytoplasm by fusing their envelope with an endosomal membrane. The molecular mechanism of this key entry step is unknown. The crystal structure of RVFV G C reveals a class II fusion protein architecture found previously in flaviviruses and alphaviruses. The structure identifies G C as the effector of membrane fusion and provides a direct view of the membrane anchor that initiates fusion. A structure of nonglycosylated G C reveals an extended conformation that may represent a fusion intermediate. Unanticipated similarities between G C and flavivirus envelope proteins reveal an evolutionary link between the two virus families and provide insights into the organization of G C in the outer shell of RVFV.