Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of the mammalian p75 neurotrophin receptor.
Rabies virus glycoprotein (RVG) is a trimeric and surface-exposed viral coat protein that has been shown to interact with the murine p75 neurotrophin receptor. We have investigated binding of RVG to p75 and describe several features that distinguish the p75-RVG interaction from conventional neurotrophin binding to p75. RVG binds mammalian but not avian p75 and does not bind to any of the Trk neurotrophin receptors. The mammalian p75 specificity of RVG binding may partly explain the phyletic specificity of rabies infection. Radioiodinated nerve growth factor (NGF) and RVG both bind to rat p75 but do not compete with each other's binding site. Although neurotrophins bind to the second and third cysteine-rich domains (CRD) of p75, RVG specifically interacts with high affinity (K(d) 30-35 pm) with the first CRD (CRD1). Substitution of Gln(33) in p75-CRD1 by Glu completely abolishes RVG binding. Our data therefore firmly establish RVG as a trimeric high affinity ligand for a non-neurotrophin binding site on p75. Interestingly, the CRD1 in another TNF/NGF family receptor was recently shown to be involved in the binding of the herpes virus glycoprotein gD, suggesting that the CRD1 of TNF/NGF family members may be a widely used binding domain for viral glycoproteins.
Langevin
Christelle
C
Laboratoire de Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique-Institut National de la Recherche Agronomique, 91198 Gif-sur-Yvette, France.
Jaaro
Hanna
H
Bressanelli
Stéphane
S
Fainzilber
Mike
M
Tuffereau
Christine
C
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral; D001665:Binding Sites; D019556:COS Cells; D002645:Chickens; D002522:Chlorocebus aethiops; D003545:Cysteine; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008322:Mammals; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010673:Pheochromocytoma; D010957:Plasmids; D011487:Protein Conformation; D011820:Rabies virus / Q000378:metabolism; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
D000956:Antigens, Viral; D006023:Glycoproteins; D008024:Ligands; D046911:Macromolecular Substances; D020800:Receptor, Nerve Growth Factor; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; D020917:Receptor, trkA; D003545:Cysteine