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 |
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Format: | Artikel |
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. |
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ISSN: | 1072-8368 1545-9993 1545-9985 |
DOI: | 10.1038/nsb0695-504 |