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

被引:16
作者
Doolittle, Russell F. [1 ]
Chen, Albert
Pandi, Leela
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA
关键词
D O I
10.1021/bi061219e
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:13962 / 13969
页数:8
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