Sunnerhagen M, Forsén S, Hoffrén A M, Drakenberg T, Teleman O, Stenflo J
Chemical Center, Lund University, Sweden.
Nat Struct Biol. 1995 Jun;2(6):504-9. doi: 10.1038/nsb0695-504.
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.
含γ-羧基谷氨酸（Gla）的凝血因子与膜的可逆结合需要Ca（2+）与10-12个Gla残基结合。本文描述了因子X的无Ca（2+）的Gla-EGF结构域对的溶液结构，该结构揭示了无Ca（2+）形式和Ca（2+）负载形式之间的显著差异。在无Ca（2+）形式中，Gla残基暴露于溶剂中，苯丙氨酸4、亮氨酸5和缬氨酸8在结构域内部形成疏水簇。在Ca（2+）负载形式中，Gla残基在结构域核心处与Ca2+结合，将三个疏水残基的侧链推向溶剂。我们提出，Ca（2+）诱导的疏水侧链暴露对于含Gla的凝血蛋白与膜的结合至关重要。
