Structure of Ca+2 -free Gla diomain shed light on membrane binding of blood coagulation proteins

Maria Sunnerhagen, Sture Forsen, Anna-Marja Hoffren, Torbjörn Drakenberg, Olle Teleman, Johan Stenflo

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144 Citations (Scopus)

Abstract

Reversible membrane binding of γ-carboxyglutamic acid (Gla)-containing coagulation factors requires Ca2+-binding to 10–12 Gla residues. Here we describe the solution structure of the Ca2+-free Gla-EGF domain pair of factor X which reveals a striking difference between the Ca2+-free and Ca2+-loaded forms. In the Ca2+-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 Ca2+-loaded form Gla residues ligate Ca22+ in the core of the domain pushing the side-chains of the three hydrophobic residues into the solvent. We propose that the Ca2+-induced exposure of hydrophobic side chains is crucial for membrane binding of Gla-containing coagulation proteins.
Original languageEnglish
Pages (from-to)504-509
JournalNature Structural Biology
Volume2
DOIs
Publication statusPublished - 1995
MoE publication typeA1 Journal article-refereed

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    Sunnerhagen, M., Forsen, S., Hoffren, A-M., Drakenberg, T., Teleman, O., & Stenflo, J. (1995). Structure of Ca+2 -free Gla diomain shed light on membrane binding of blood coagulation proteins. Nature Structural Biology, 2, 504-509. https://doi.org/10.1038/nsb0695-504