Adenovirus type 9 fiber knob binds to the coxsackie B virus-adenovirus receptor (CAR) with lower affinity than fiber knobs of other CAR-binding adenovirus serotypes
Adenovirus type 9 fiber knob binds to the coxsackie B virus-adenovirus receptor (CAR) with lower affinity than fiber knobs of other CAR-binding adenovirus serotypes
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DOI：
10.1128/jvi.75.15.7210-7214.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Santis, G
中科院分区：
文献类型：
--
作者：
Kirby, I;Lord, R;Santis, G
柯萨奇B病毒和腺病毒(Ad)受体(CAR)作为多种Ad血清型的附着受体，我们发现与Ad5和AD12纤维节以及AD41(Ad41L)长纤维节的结合相比，AdSertype 9(Ad9)纤维节与CAR的亲和力大大降低，Ad9纤维节中的Asp222被Ad5、AD12和Ad41L中保守的赖氨酸取代后显著增加了Ad9纤维节与CAR的结合，而Ad5中相应的替换(Lys442Asp)显著降低了Ad5的结合。因此，Ad9中天冬氨酸残基的存在至少部分地解释了Ad9纤维旋钮的CAR结合亲和力降低。CAR的定点突变表明，CAR残基Leu73、Lys121和/或Lys123是关键的接触残基，Tyr80和Tyr83外围参与与Ad5、Ad9、Ad12和Ad41L纤维结节的结合。野生型CAR以及Tyr80和Tyr83CAR突变体的总亲和力以及结合和解离速率常数在不同的血清型之间存在差异，表明它们的结合模式虽然相似，但并不完全相同。
The coxsackie B virus and adenovirus (Ad) receptor (CAR) functions as an attachment receptor for multiple Ad serotypes, Here we show that the Ad serotype 9 (Ad9) fiber knob binds to CAR with much reduced affinity compared to the binding by Ad5 and Ad12 fiber knobs as well as the knob of the long fiber of Ad41 (Ad41L), Substitution of Asp222 in Ad9 fiber knob with a lysine that is conserved in Ad5, Ad12, and Ad41L substantially improved Ad9 fiber knob binding to CAR, while the corresponding substitution in Ad5 (Lys442Asp) significantly reduced Ad5 binding. The presence of an aspartic acid residue in Ad9 therefore accounts, at least in part, for the reduced CAR binding affinity of the Ad9 fiber knob. Site-directed mutagenesis of CAR revealed that CAR residues Leu73 and Lys121 and/or Lys123 are critical contact residues, with Tyr80 and Tyr83 being peripherally involved in the binding interaction with the Ad5, Ad9, Ad12, and Ad41L fiber knobs. The overall affinities and the association and dissociation rate constants for wild-type CAR as well as Tyr80 and Tyr83 CAR mutants differed between the serotypes, indicating that their binding modes, although similar, are not identical.