 |
|
Title
|
|
Structure of the Ca(2+)-free Gla domain sheds light on membrane binding of blood coagulation proteins.
|
|
|
Authors
|
|
M.Sunnerhagen,
S.Forsén,
A.M.Hoffrén,
T.Drakenberg,
O.Teleman,
J.Stenflo.
|
|
|
Ref.
|
|
Nat Struct Biol, 1995,
2,
504-509.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Reversible membrane binding of gamma-carboxyglutamic acid (Gla)-containing
coagulation factors requires Ca(2+)-binding to 10-12 Gla residues. Here we
describe the solution structure of the Ca(2+)-free Gla-EGF domain pair of factor
x which reveals a striking difference between the Ca(2+)-free and Ca(2+)-loaded
forms. In the Ca(2+)-free form Gla residues are exposed to solvent and Phe 4,
Leu 5 and Val 8 form a hydrophobic cluster in the interior of the domain. In the
Ca(2+)-loaded form Gla residues ligate Ca2+ in the core of the domain pushing
the side-chains of the three hydrophobic residues into the solvent. We propose
that the Ca(2+)-induced exposure of hydrophobic side chains is crucial for
membrane binding of Gla-containing coagulation proteins.
|
|
|
|