Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of the mammalian p75 neurotrophin receptor

Christelle Langevin, Hanna Jaaro, Stéphane Bressanelli, Mike Fainzilber, Christine Tuffereau

Research output: Contribution to journalArticlepeer-review

Abstract

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 (Kd 3035 pM) with the first CRD (CRD1). Substitution of Gln33 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.

Original languageEnglish (US)
Pages (from-to)37655-37662
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number40
DOIs
StatePublished - Oct 4 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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