Publication Date:
2008-03-29
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, I-Mei -- Zhang, Wei -- Holdaway, Heather A -- Li, Long -- Kostyuchenko, Victor A -- Chipman, Paul R -- Kuhn, Richard J -- Rossmann, Michael G -- Chen, Jue -- 1-U54-AI-057153/AI/NIAID NIH HHS/ -- AI055672/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Mar 28;319(5871):1834-7. doi: 10.1126/science.1153264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, 915 West State Street, Purdue University, West Lafayette, IN 47907-2054, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18369148" target="_blank"〉PubMed〈/a〉
Keywords:
Cryoelectron Microscopy
;
Crystallography, X-Ray
;
Dengue Virus/*chemistry/growth & development/metabolism/*ultrastructure
;
Dimerization
;
Endoplasmic Reticulum/virology
;
Furin/metabolism
;
Hydrogen-Ion Concentration
;
Image Processing, Computer-Assisted
;
Membrane Fusion
;
Protein Conformation
;
Viral Envelope Proteins/*chemistry/metabolism
;
Viral Fusion Proteins/chemistry/metabolism
;
Viral Matrix Proteins/*chemistry/metabolism
;
Virion/metabolism/ultrastructure
;
trans-Golgi Network/metabolism/virology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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