British Heart Foundation Glasgow Cardiovascular Research Centre, College of Medical, Veterinary and Life Sciences, University of Glasgow, 126 University Place, Glasgow G128TA, United Kingdom.
J Virol. 2011 Oct;85(20):10914-9. doi: 10.1128/JVI.05382-11. Epub 2011 Aug 17.
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.
静脉注射腺病毒 5(Ad5)后肝细胞的转导是通过凝血因子 X(FX)与六邻体之间的相互作用介导的。FX 丝氨酸蛋白酶(SP)结构域通过结合硫酸乙酰肝素蛋白聚糖(HSPG)将 Ad5/FX 复合物连接到肝细胞上。在这里,我们确定了 FX 的关键 HSPG 相互作用残基。我们通过修饰 SP 结构域中的七个残基生成了一个 FX 突变体。表面等离子体共振表明,突变不影响与 Ad5 的结合。FX 介导的 HSPG 相关细胞结合和转导被完全阻断。因此,SP 结构域中的一簇碱性氨基酸介导 Ad/FX 复合物的表面相互作用。