10.1021/bi980522f.s001
Andreas Muranyi
Andreas
Muranyi
Bryan E. Finn
Bryan E.
Finn
Garry P. Gippert
Garry P.
Gippert
Sture Forsén
Sture
Forsén
Johan Stenflo
Johan
Stenflo
Torbjörn Drakenberg
Torbjörn
Drakenberg
Solution Structure of the N-Terminal EGF-like Domain from Human Factor VII<sup>†</sup><sup>,</sup><sup>‡</sup>
American Chemical Society
1998
TF interaction surface
epidermal growth factor
FVII
EGF 1
coagulation factor VIIa
Amino acid side chains
EGF 1 domains
binding
EGF 1 domain
apo EGF 1
1998-07-03 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Solution_Structure_of_the_N-Terminal_EGF-like_Domain_from_Human_Factor_VII_sup_sup_sup_sup_sup_sup_/3588459
Blood coagulation is initiated by Ca<sup>2+</sup>-dependent binding of coagulation factor VIIa (FVIIa)
to its cofactor, tissue factor (TF). The TF:FVIIa complex activates factors IX and X, ultimately leading
to the formation of thrombin and the coagulation of blood. FVII consists of an N-terminal γ-carboxyglutamic-acid-containing (Gla) domain followed by two epidermal growth factor (EGF) like domains, the
first of which can bind one Ca<sup>2+</sup> ion (<i>K</i><sub>d</sub> ≈ 150 μM) and a C-terminal serine protease domain. Using <sup>1</sup>H
nuclear magnetic resonance spectroscopy, we have determined the solution structure of a synthetic
N-terminal EGF-like domain (EGF1) of human FVII (residues 45−85) in the absence of Ca<sup>2+</sup>. A
comparison of this structure of apo EGF1 with the Ca<sup>2+</sup>-bound EGF1 in the complex of FVIIa and TF
[Banner, D. W., et al. (1996) <i>Nature 380</i>, 41−46] suggests that the structural changes in the EGF1 domain
upon Ca<sup>2+</sup> binding are minor and are concentrated near the Ca<sup>2+</sup>-binding site, which is facing away from
the TF interaction surface. Amino acid side chains that are crucial for the binding of FVII to TF show
a similar conformation in both structures and are therefore unlikely to directly influence the Ca<sup>2+</sup>-dependent
binding of FVII to TF. As Ca<sup>2+</sup> binding to EGF1 does not lead to a conformational change in the residues
constituting the interaction surface for binding to TF, our results are consistent with the idea that the
altered orientation between the Gla and EGF1 domains that result from Ca<sup>2+</sup> binding is responsible for
the increased affinity of FVII/FVIIa for TF.