title: Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR.
abstract: Binding of virus particles to specific host cell surface receptors is known to be an obligatory step in infection even though the molecular basis for these interactions is not well characterized. The crystal structure of the adenovirus fiber knob domain in complex with domain I of its human cellular receptor, coxsackie and adenovirus receptor (CAR), is presented here. Surface-exposed loops on knob contact one face of CAR, forming a high-affinity complex. Topology mismatches between interacting surfaces create interfacial solvent-filled cavities and channels that may be targets for antiviral drug therapy. The structure identifies key determinants of binding specificity, which may suggest ways to modify the tropism of adenovirus-based gene therapy vectors.
authors.affiliation: Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Bewley
authors.forename: K
authors.initials: K
authors.lastname: Springer
authors.forename: Y B
authors.initials: YB
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Freimuth
authors.forename: J M
authors.initials: JM
authors.lastname: Flanagan
mesh_terms: D000260:Adenoviruses, Human / Q000737:chemistry / Q000378:metabolism*; D019943:Amino Acid Substitution; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism*; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D011994:Recombinant Proteins; C018315:hexon capsid protein, Adenovirus