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Originally published In Press as doi:10.1074/jbc.M801470200 on July 2, 2008

J. Biol. Chem., Vol. 283, Issue 39, 26452-26460, September 26, 2008
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The Dynamic Envelope of a Fusion Class II Virus

E3 DOMAIN OF GLYCOPROTEIN E2 PRECURSOR IN SEMLIKI FOREST VIRUS PROVIDES A UNIQUE CONTACT WITH THE FUSION PROTEIN E1*

Shang-Rung Wu1, Lars Haag2, Mathilda Sjöberg, Henrik Garoff, and Lena Hammar

From the Department of Biosciences and Nutrition, Karolinska Institutet, SE-14157 Huddinge, Sweden

In alphaviruses, here represented by Semliki Forest virus, infection requires an acid-responsive spike configuration to facilitate membrane fusion. The creation of this relies on the chaperon function of glycoprotein E2 precursor (p62) and its maturation cleavage into the small external E3 and the membrane-anchored E2 glycoproteins. To reveal how the E3 domain of p62 exerts its control of spike functions, we determine the structure of a p62 cleavage-impaired mutant virus particle (SQL) by electron cryomicroscopy. A comparison with the earlier solved wild type virus structure reveals that the E3 domain of p62SQL forms a bulky side protrusion in the spike head region. This establishes a gripper over part of domain II of the fusion protein, with a cotter-like connection downward to a hydrophobic cluster in its central β-sheet. This finding reevaluates the role of the precursor from being only a provider of a shield over the fusion loop to a structural playmate in formation of the fusogenic architecture.


Received for publication, February 22, 2008 , and in revised form, June 9, 2008.

* This work has been supported by Swedish Medical Research Council, European Union 6th Framework Program (Project 512740) and by The Swedish Knowledge Foundation together with Crystal Research AB (Lund, Sweden), through the Industrial Ph.D. program in Medical Bioinformatics (to S.-R. W.) at the Karolinska Institutet, Sweden. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

2 Present address: Vironova AB, SE-13134 Nacka, Sweden.

1 To whom correspondence should be addressed. Tel.: 46-8-608-9122; Fax: 46-8-774-5538; E-mail: Shang-Rung.Wu{at}ki.se.


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