Structure of the Ca2+-free GLA domain sheds light on membrane binding of blood coagulation proteins

Reversible membrane binding of γ-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+ -...

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Veröffentlicht in:Nature Structural Biology 1995-06, Vol.2 (6), p.504-509
Hauptverfasser: Sunnerhagen, Maria, Forsén, Sture, Hoffrén, Anna-Marja, Drakenberg, Torbjörn, Teleman, Olle, Stenflo, Johan
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Sprache:eng
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Zusammenfassung:Reversible membrane binding of γ-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 2+ 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.
ISSN:1072-8368
1545-9993
1545-9985
DOI:10.1038/nsb0695-504