A Cluster of Basic Amino Acids in the Factor X Serine Protease Mediates Surface Attachment of Adenovirus/FX Complexes
A Cluster of Basic Amino Acids in the Factor X Serine Protease Mediates Surface Attachment of Adenovirus/FX Complexes
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DOI：
10.1128/jvi.05382-11
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发表时间：
2011-10-01
影响因子：
5.4
通讯作者：
Baker, Andrew H.
中科院分区：
文献类型：
--
作者：
Duffy, Margaret R.;Bradshaw, Angela C.;Baker, Andrew H.
静脉内施用腺病毒5（Ad 5）后的肝细胞转导由凝血因子X（FX）和六邻体之间的相互作用介导。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Ad 5/FX复合物拴系到肝细胞。在这里，我们确定了关键的HSPG相互作用的FX残基。我们通过修饰SP结构域中的7个残基产生FX突变体。表面等离子体共振证实突变不影响与Ad 5的结合。FX介导的HSPG相关细胞结合和转导被消除。因此，SP结构域中的碱性氨基酸簇介导Ad/FX复合物的表面相互作用。
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.