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

Research output: Contribution to journalArticleScientificpeer-review

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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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Blood Coagulation
Blood Proteins
Factor X
Blood Coagulation Factors
Membranes
Epidermal Growth Factor
Acids
Proteins

Cite this

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
Sunnerhagen, Maria ; Forsen, Sture ; Hoffren, Anna-Marja ; Drakenberg, Torbjörn ; Teleman, Olle ; Stenflo, Johan. / Structure of Ca+2 -free Gla diomain shed light on membrane binding of blood coagulation proteins. In: Nature Structural Biology. 1995 ; Vol. 2. pp. 504-509.
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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.",
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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, vol. 2, pp. 504-509. https://doi.org/10.1038/nsb0695-504

Structure of Ca+2 -free Gla diomain shed light on membrane binding of blood coagulation proteins. / Sunnerhagen, Maria; Forsen, Sture; Hoffren, Anna-Marja; Drakenberg, Torbjörn; Teleman, Olle; Stenflo, Johan.

In: Nature Structural Biology, Vol. 2, 1995, p. 504-509.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Sunnerhagen, Maria

AU - Forsen, Sture

AU - Hoffren, Anna-Marja

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AU - Teleman, Olle

AU - Stenflo, Johan

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