Modeling a sialic acid binding pocket in the external loops of JC virus VP1

J Biol Chem. 2004 Nov 19;279(47):49172-6. doi: 10.1074/jbc.M409326200. Epub 2004 Sep 3.

Abstract

JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has a restricted cell tropism that is caused partly by the initial interaction between the virus and sialic acid-containing host cell receptors. To identify the molecular interactions between the virus and its cellular receptor, we used a combined approach of site-directed mutagenesis and homology-based molecular modeling. A model of the major viral capsid protein VP1 based on sequence alignment with other closely related polyomaviruses allowed us to target specific amino acids in the extracellular loops of VP1 for mutagenesis. An analysis of the growth rates of 17 point mutants led to the identification of VP1 amino acids that are critical in virus-host cell receptor interactions. Molecular dynamics simulations were then used to build and confirm a model of the interaction between VP1 and the sialic acid component of the JCV receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Capsid
  • Capsid Proteins / chemistry*
  • Cell Line
  • Cell Nucleus / virology
  • Computer Simulation
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Microscopy, Electron
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • N-Acetylneuraminic Acid / chemistry*
  • Neuroglia / cytology
  • Neuroglia / virology
  • Plasmids / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Time Factors
  • Transfection

Substances

  • Capsid Proteins
  • VP1 protein, polyomavirus
  • N-Acetylneuraminic Acid