Modeling a Sialic Acid Binding Pocket in the External Loops of JC Virus VP1

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 vir...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-11, Vol.279 (47), p.49172-49176
Main Authors: Gee, Gretchen V, Tsomaia, Natia, Mierke, Dale F, Atwood, Walter J
Format: Article
Language:English
Subjects:
Binding Sites
Capsid
Capsid Proteins - chemistry
Cell Line
Cell Nucleus - virology
Computer Simulation
Fluorescent Antibody Technique, Indirect
Humans
JC virus
Microscopy, Electron
Models, Molecular
Mutagenesis, Site-Directed
N-Acetylneuraminic Acid - chemistry
Neuroglia - cytology
Neuroglia - virology
Plasmids - metabolism
Polyomavirus
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Time Factors
Transfection
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M409326200