Article

Structure of the immature dengue virus at low pH primes proteolytic maturation.

Department of Biological Sciences, 915 West State Street, Purdue University, West Lafayette, IN 47907-2054, USA.
Science (Impact Factor: 31.48). 04/2008; 319(5871):1834-7. DOI: 10.1126/science.1153264
Source: PubMed

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.

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