Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion

Journal of Cell Biology - Tập 171 Số 1 - Trang 111-120 - 2005
Maofu Liao1, Margaret Kielian2
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461

Tóm tắt

Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. We demonstrate that exogenous domain III can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and infection. Domain III binds stably to the fusion protein, thus preventing the foldback reaction and blocking the lipid mixing step of fusion. Our data reveal the existence of a relatively long-lived core trimer intermediate with which domain III interacts to initiate membrane fusion. These novel inhibitors of the class II fusion proteins show cross-inhibition within the virus genus and suggest that the domain III–core trimer interaction can serve as a new target for the development of antiviral reagents.

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Thông tin
Thông tin xuất bản

Journal of Cell Biology

Tập 171 Số 1

111-120

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