Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole.
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 gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly.
Doolittle
Russell F
RF
Department of Chemistry and Biochemistry and Division of Biology, University of California at San Diego, La Jolla, California 92093-0314, USA. rdoolittle@ucsd.edu
Chen
Albert
A
Pandi
Leela
L
D000818:Animals; D002645:Chickens; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D009842:Oligopeptides; D005337:Fibrin; D005340:Fibrinogen