3E1I

Crystal Structure of BbetaD432A Variant Fibrinogen Fragment D with the Peptide Ligand Gly-His-Arg-Pro-amide

3E1I の概要

• エントリーDOI: 10.2210/pdb3e1i/pdb
• 関連するPDBエントリー: 1LTJ 1RE3
• 分子名称: Fibrinogen alpha chain, Fibrinogen beta chain, Fibrinogen gamma chain, ... (7 entities in total)
• 機能のキーワード: blood coagulation, disease mutation, glycoprotein, phosphoprotein, secreted, pyrrolidone carboxylic acid, sulfation, blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 169886.48

構造登録者

Bowley, S.R.,Lord, S.T. (登録日: 2008-08-04, 公開日: 2009-01-13, 最終更新日: 2024-11-20)

主引用文献

Bowley, S.R.,Lord, S.T.
Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".
Blood, 113:4425-4430, 2009

PubMed 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 normal fibrinogen. Scanning electron microscopy showed no significant differences between the clots of BbetaD432A and normal, but the thrombin-derived clots had thicker fibers than clots obtained from batroxobin, suggesting that cleavage of FpB is more important than "B:b" interactions. We conclude that hole "b" and "B:b" knob-hole binding per se have no influence on fibrin polymerization.

PubMed: 19075185
DOI: 10.1182/blood-2008-09-178178

実験手法

X-RAY DIFFRACTION (2.3 Å)