Differences in binding specificity for the homologous γ- and β-chain "Holes" on fibrinogen:: Exclusive binding of Ala-His-Arg-Pro-amide by the β-chain hole
Differences in binding specificity for the homologous γ- and β-chain "Holes" on fibrinogen:: Exclusive binding of Ala-His-Arg-Pro-amide by the β-chain hole
复制标题
DOI：
10.1021/bi061219e
复制
发表时间：
2006-11-28
期刊：
影响因子：
2.9
通讯作者：
Pandi, Leela
中科院分区：
文献类型：
--
作者：
Doolittle, Russell F.;Chen, Albert;Pandi, Leela
所有已知的哺乳动物胰高血糖素的β-链氨基末端序列开始以序列Gly-His-Arg-Pro-（GHRP-）开始，但鸡纤维蛋白中的同源序列以序列Ala-His-Arg-Pro-（AHRP-）开始。尽管如此，鸡纤维蛋白原结合的合成肽GHRPam，和以前报道的晶体结构已经揭示，该结合是完全符合所观察到的人GHRPam-片段D复合物。我们现在报告，人纤维蛋白原，这是已知的不结合APRP，结合合成肽AHRPam。此外，与来自人纤维蛋白原的片段D复合的AHRPam的晶体结构显示，AHRPam仅与β链孔结合，并且与GHRPam不同，完全不与同源γ链孔结合。这种差异可以归因于丙氨酸残基的甲基与γ C孔中的关键羧基发生冲突，但被容纳在更宽敞的β C孔中，其中等价羧基的位置更灵活。
The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gamma C hole but being accommodated in the roomier beta C hole where the equivalent carboxyl is situated more flexibly.