title: The structure of human rhinovirus 16.
abstract: BACKGROUND
  Rhinoviruses and the homologous polioviruses have hydrophobic pockets below their receptor-binding sites, which often contain unidentified electron density ('pocket factors'). Certain antiviral compounds also bind in the pocket, displacing the pocket factor and inhibiting uncoating. However, human rhinovirus (HRV)14, which belongs to the major group of rhinoviruses that use intercellular adhesion molecule-1 (ICAM-1) as a receptor, has an empty pocket. When antiviral compounds bind into the empty pocket of HRV14, the roof of the pocket, which is also the floor of the receptor binding site (the canyon), is deformed, preventing receptor attachment. The role of the pocket in viral infectivity is not known.
  
  
  RESULTS
  We have determined the structure of HRV16, another major receptor group rhinovirus serotype, to atomic resolution. Unlike HRV14, the pockets contain electron density resembling a fatty acid, eight or more carbon atoms long. Binding of the antiviral compound WIN 56291 does not cause deformation of the pocket, although it does prevent receptor attachment.
  
  
  CONCLUSIONS
  We conjecture that the binding of the receptor to HRV16 can occur only when the pocket is temporarily empty, when it is possible for the canyon floor to be deformed downwards into the pocket. We further propose that the role of the pocket factor is to stabilize virus in transit from one host cell to the next, and that binding of ICAM-1 traps the pocket in the empty state, destabilizing the virus as required for uncoating.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
authors.forename: M A
authors.initials: MA
authors.lastname: Oliveira
authors.forename: R
authors.initials: R
authors.lastname: Zhao
authors.forename: W M
authors.initials: WM
authors.lastname: Lee
authors.forename: M J
authors.initials: MJ
authors.lastname: Kremer
authors.forename: I
authors.initials: I
authors.lastname: Minor
authors.forename: R R
authors.initials: RR
authors.lastname: Rueckert
authors.forename: G D
authors.initials: GD
authors.lastname: Diana
authors.forename: D C
authors.initials: DC
authors.lastname: Pevear
authors.forename: F J
authors.initials: FJ
authors.lastname: Dutko
authors.forename: M A
authors.initials: MA
authors.lastname: McKinlay
mesh_terms: D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000633:toxicity; D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology; D012229:Rhinovirus / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D017386:Sequence Homology, Amino Acid
chemical_list: D000998:Antiviral Agents; D036022:Capsid Proteins; D015815:Cell Adhesion Molecules; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1