title: Cryo-EM structure of the mature dengue virus at 3.5-Å resolution.
abstract: Regulated by pH, membrane-anchored proteins E and M function during dengue virus maturation and membrane fusion. Our atomic model of the whole virion from cryo-electron microscopy at 3.5-Å resolution reveals that in the mature virus at neutral extracellular pH, the N-terminal 20-amino-acid segment of M (involving three pH-sensing histidines) latches and thereby prevents spring-loaded E fusion protein from prematurely exposing its fusion peptide. This M latch is fastened at an earlier stage, during maturation at acidic pH in the trans-Golgi network. At a later stage, to initiate infection in response to acidic pH in the late endosome, M releases the latch and exposes the fusion peptide. Thus, M serves as a multistep chaperone of E to control the conformational changes accompanying maturation and infection. These pH-sensitive interactions could serve as targets for drug discovery.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles-UCLA, Los Angeles, California, USA.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Ge
authors.forename: Xuekui
authors.initials: X
authors.lastname: Yu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Brannan
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Bi
authors.forename: Qinfen
authors.initials: Q
authors.lastname: Zhang
authors.forename: Stan
authors.initials: S
authors.lastname: Schein
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000330:Aedes / Q000821:virology; D000818:Animals; D002460:Cell Line; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000378:metabolism; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D053585:Virus Attachment; D021601:trans-Golgi Network / Q000378:metabolism / Q000821:virology
chemical_list: D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C072281:E protein TH Sman, Dengue virus