The Structure of the Fusion Glycoprotein of Newcastle Disease Virus Suggests a Novel Paradigm for the Molecular Mechanism of Membrane Fusion
| Autor: | P.A. Tulloch, Brian J. Smith, Lynne J. Lawrence, J.L. McKimm-Breschkin, Jeffrey J Gorman, Peter M. Colman, Michael C. Lawrence, Lin Chen |
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| Rok vydání: | 2001 |
| Předmět: |
Viral protein
Molecular Sequence Data Newcastle disease virus Hemagglutinin (influenza) Biology medicine.disease_cause Crystallography X-Ray Membrane Fusion Protein structure Structural Biology fusion protein medicine Amino Acid Sequence Protein Structure Quaternary Molecular Biology X-ray crystallography Coiled coil Lipid bilayer fusion Viral membrane Fusion protein Heptad repeat Crystallography Paramyxoviridae biology.protein Biophysics Sequence Alignment Viral Fusion Proteins |
| Zdroj: | Structure. 9(3):255-266 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(01)00581-0 |
| Popis: | Background: Membrane fusion within the Paramyxoviridae family of viruses is mediated by a surface glycoprotein termed the "F", or fusion, protein. Membrane fusion is assumed to involve a series of structural transitions of F from a metastable (prefusion) state to a highly stable (postfusion) state. No detail is available at the atomic level regarding the metastable form of these proteins or regarding the transitions accompanying fusion. Results: The three-dimensional structure of the fusion protein of Newcastle disease virus (NDV-F) has been determined. The trimeric NDV-F molecule is organized into head, neck, and stalk regions. The head is comprised of a highly twisted β domain and an additional immunoglobulin-like β domain. The neck is formed by the C-terminal extension of the heptad repeat region HR-A, capped by a four-helical bundle. The C terminus of HR-A is encased by a further helix HR-C and a 4-stranded β sheet. The stalk is formed by the remaining visible portion of HR-A and by polypeptide immediately N-terminal to the C-terminal heptad repeat region HR-B. An axial channel extends through the head and neck and is fenestrated by three large radial channels located approximately at the head–neck interface. Conclusion: We propose that prior to fusion activation, the hydrophobic fusion peptides in NDV-F are sequestered within the radial channels within the head, with the central HR-A coiled coil being only partly formed. Fusion activation then involves, inter alia, the assembly of a complete HR-A coiled coil, with the fusion peptides and transmembrane anchors being brought into close proximity. The structure of NDV-F is fundamentally different than that of influenza virus hemagglutinin, in that the central coiled coil is in the opposite orientation with respect to the viral membrane. |
| Databáze: | OpenAIRE |
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