Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".

ABSTRACT: Fibrinogen residue Bbeta432Asp is part of hole "b" that interacts with knob "B," whose sequence starts with Gly-His-Arg-Pro-amide (GHRP). Because previous studies showed BbetaD432A has normal polymerization, we hypothesized that Bbeta432Asp is not critical for knob "B" binding and that new knob-hole interactions would compensate for the loss of this Asp residue. To test this hypothesis, we solved the crystal structure of fragment D from BbetaD432A. Surprisingly, the structure (rfD-BbetaD432A+GH) showed the peptide GHRP was not bound to hole "b." We then re-evaluated the polymerization of this variant by examining clot turbidity, clot structure, and the rate of FXIIIa cross-linking. The turbidity and the rate of gamma-gamma dimer formation for BbetaD432A were indistinguishable compared with

SUBMITTER: Bowley SR 

PROVIDER: S-EPMC2676095 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature