TY - JOUR
T1 - Structure of the immature dengue virus at low pH primes proteolytic maturation
AU - Yu, I. Mei
AU - Zhang, Wei
AU - Holdaway, Heather A.
AU - Li, Long
AU - Kostyuchenko, Victor A.
AU - Chipman, Paul R.
AU - Kuhn, Richard J.
AU - Rossmann, Michael G.
AU - Chen, Jue
PY - 2008/3/28
Y1 - 2008/3/28
N2 - 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.
AB - 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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U2 - 10.1126/science.1153264
DO - 10.1126/science.1153264
M3 - Article
C2 - 18369148
AN - SCOPUS:41349112304
SN - 0036-8075
VL - 319
SP - 1834
EP - 1837
JO - Science
JF - Science
IS - 5871
ER -