title: Structure of the immature dengue virus at low pH primes proteolytic maturation.
abstract: Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo-electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.
authors: Department of Biological Sciences, 915 West State Street, Purdue University, West Lafayette, IN 47907-2054, USA.
authors: I-Mei
authors: IM
authors: Yu
authors: Wei
authors: W
authors: Zhang
authors: Heather A
authors: HA
authors: Holdaway
authors: Long
authors: L
authors: Li
authors: Victor A
authors: VA
authors: Kostyuchenko
authors: Paul R
authors: PR
authors: Chipman
authors: Richard J
authors: RJ
authors: Kuhn
authors: Michael G
authors: MG
authors: Rossmann
authors: Jue
authors: J
authors: Chen
mesh_terms: D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D003716:Dengue Virus / Q000737:chemistry* / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000821:virology; D045683:Furin / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D008561:Membrane Fusion; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure; D021601:trans-Golgi Network / Q000378:metabolism / Q000821:virology
chemical_list: C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; D045683:Furin