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.
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 (G1-439) lacking the transmembrane and intracytoplasmic domains (residues 440-505). It is shown that, whatever the extracellular pH, G1-439 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 (G1-461) 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.
Gaudin
Y
Y
Moreira
S
S
B N Jean
J
J
Blondel
D
D
Flamand
A
A
Tuffereau
C
C
D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D017510:Protein Folding; D011818:Rabies / Q000821:virology*; D011820:Rabies virus / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology; D014779:Virus Replication
D000956:Antigens, Viral; D006023:Glycoproteins; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus