Structural Analysis of the Mechanism of Adenovirus Binding to Its Human Cellular Receptor, CAR

• Published in: Science (American Association for the Advancement of Science) Vol. 286; no. 5444; pp. 1579 - 1583
• Main Authors: Bewley, Maria C., Springer, Karen, Zhang, Yian-Biao, Freimuth, Paul, Flanagan, John M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 19.11.1999; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Adenovirus; Adenovirus diseases; Adenovirus infections; Adenoviruses; Adenoviruses, Human - chemistry; Adenoviruses, Human - metabolism; Amino Acid Substitution; Atoms; Binding Sites; Biological and medical sciences; Capsid - chemistry; Capsid - metabolism; Capsid Proteins; Cellular biology; Census agricultural regions; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Crystallization; Crystallography, X-Ray; Crystals; Delivery Systems; Drug Therapy; Fundamental and applied biological sciences. Psychology; Human adenovirus; Hybrid cars; Hydrogen Bonding; Infections; Microbiology; Models, Molecular; Molecules; Monomers; Motor Vehicles; Mutagenesis; Observation; Protein Binding; Protein Conformation; Protein Structure, Secondary; Receptors; Receptors, Virus - chemistry; Receptors, Virus - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Structural Analysis (Linguistics); Structural Analysis (Science); Thermodynamics; Topology; Virology; Virus diseases; Viruses; United States; Human; Adenovirus 12; Adenoviridae; Molecular interaction; Binding site; Host virus relation; Adhesion; Modeling; Structure function relationship; Spicule; Cell surface; Virus; Three dimensional structure; Human adenovirus; Mastadenovirus; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.286.5444.1579

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 1 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.