5evm
Crystal Structure of Nipah Virus Fusion Glycoprotein in the Prefusion StateCrystal Structure of Nipah Virus Fusion Glycoprotein in the Prefusion State
Structural highlights
FunctionFUS_NIPAV Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (F protein) probably interacts with HN at the virion surface. Upon HN binding to its cellular receptor, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between cell and virion membranes. Later in infection, F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (By similarity). Publication Abstract from PubMedNipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein. Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly.,Xu K, Chan YP, Bradel-Tretheway B, Akyol-Ataman Z, Zhu Y, Dutta S, Yan L, Feng Y, Wang LF, Skiniotis G, Lee B, Zhou ZH, Broder CC, Aguilar HC, Nikolov DB PLoS Pathog. 2015 Dec 8;11(12):e1005322. doi: 10.1371/journal.ppat.1005322., eCollection 2015 Dec. PMID:26646856[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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