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Structure of the Parainfluenza Virus 5 F Protein in its Metastable, Pre-fusion ConformationStructure of the Parainfluenza Virus 5 F Protein in its Metastable, Pre-fusion Conformation
Structural highlights
FunctionFUS_PIV5 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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEnveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein. Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation.,Yin HS, Wen X, Paterson RG, Lamb RA, Jardetzky TS Nature. 2006 Jan 5;439(7072):38-44. PMID:16397490[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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