Journal of General Virology, Vol 80, 1647-1656, Copyright © 1999 by Society for General Microbiology

ARTICLES

Soluble ectodomain of rabies virus glycoprotein expressed in eukaryotic cells folds in a monomeric conformation that is antigenically distinct from the native state of the complete, membrane-anchored glycoprotein

Y Gaudin, S Moreira, J Benejean, D Blondel, A Flamand and C Tuffereau
Laboratoire de genetique des virus du CNRS, 91198 Gif sur Yvette Cedex, France

Rabies virus glycoprotein (G) is a trimeric type I transmembrane glycoprotein that mediates both virus receptor recognition and low pH-induced membrane fusion. G can assume three different states: the 'native' state (N) detected at the virus surface, which is responsible for receptor binding, the activated hydrophobic state (A), which interacts with the target membrane as a first step in the fusion process, and the fusion-inactive conformation (I). These three states, which are structurally different, are in a pH-dependent equilibrium. This equilibrium is shifted toward the I state at low pH. This paper includes an investigation of the structure of the ectodomain of the PV strain of rabies virus when it is synthesized as a soluble form (G(1--439)) lacking the transmembrane and intracytoplasmic domains (residues 440--505). It is shown that, whatever the extracellular pH, G(1--439) is secreted as a monomer that has the antigenic characteristics of the I state. This I-like state is not acquired in the acidic compartments of the Golgi but directly in the endoplasmic reticulum. Finally, membrane anchorage by the G transmembrane domain (G(1--461)) is sufficient for the G ectodomain to be folded into the native N form. These results emphasize the role of the G transmembrane domain in the correct folding of the ectodomain.

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