title: A cluster of basic amino acids in the factor X serine protease mediates surface attachment of adenovirus/FX complexes.
abstract: Hepatocyte transduction following intravenous administration of adenovirus 5 (Ad5) is mediated by interaction between coagulation factor X (FX) and the hexon. The FX serine protease (SP) domain tethers the Ad5/FX complex to hepatocytes through binding heparan sulfate proteoglycans (HSPGs). Here, we identify the critical HSPG-interacting residues of FX. We generated an FX mutant by modifying seven residues in the SP domain. Surface plasmon resonance demonstrated that mutations did not affect binding to Ad5. FX-mediated, HSPG-associated cell binding and transduction were abolished. A cluster of basic amino acids in the SP domain therefore mediates surface interaction of the Ad/FX complex.
authors.affiliation: British Heart Foundation Glasgow Cardiovascular Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, 126 University Place, Glasgow G128TA, United Kingdom.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Duffy
authors.forename: Angela C
authors.initials: AC
authors.lastname: Bradshaw
authors.forename: Alan L
authors.initials: AL
authors.lastname: Parker
authors.forename: John H
authors.initials: JH
authors.lastname: McVey
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D019943:Amino Acid Substitution / Q000235:genetics; D024361:Amino Acids, Basic / Q000235:genetics / Q000378:metabolism*; D005170:Factor X / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020349:Surface Plasmon Resonance
chemical_list: D024361:Amino Acids, Basic; D019812:Heparan Sulfate Proteoglycans; D050505:Mutant Proteins; D005170:Factor X