Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins

Huang MD.; Rigby AC.; Morelli X.; Grant MA.; Huang GQ.; Furie B.; Seaton B.; Furie BC.

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Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins

机译：维生素K依赖蛋白的Gla结构域结合膜的结构基础

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In a calcium-dependent interaction critical for blood coagulation, vitamin K dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via gamma-carboxyglutamic acid rich (Gla) domains. Gla domain mediated protein-membrane interaction is required for generation of thrombin, the terminal enzyme in the coagulation cascade, on a physiologic time scale. We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain. The serine head group binds Gla domain bound calcium ions and Gla residues 17 and 21, fixed elements of the Gla domain fold, predicting the structural basis for phosphatidylserine specificity among Gla domains. Gla domains provide a unique mechanism for protein-phospholipid membrane interaction. Increasingly Gla domains are being identified in proteins unrelated to blood coagulation. Thus, this membrane-binding mechanism may be important in other physiologic processes. [References: 45]

机译：在对血液凝固至关重要的钙依赖性相互作用中，维生素K依赖性血液凝固蛋白通过富含γ-羧基谷氨酸的（Gla）结构域结合含有磷脂酰丝氨酸的细胞膜。在生理学时间尺度上，Gla结构域介导的蛋白膜相互作用对于凝血酶（凝血级联反应中的末端酶）的产生是必需的。我们通过X射线晶体学和NMR光谱确定了牛凝血酶原Gla结构域中的溶血磷脂酰丝氨酸结合位点。丝氨酸头部基团结合Gla结构域结合的钙离子和Gla残基17和21，Gla结构域的固定元件折叠，从而预测Gla结构域中磷脂酰丝氨酸特异性的结构基础。 Gla结构域为蛋白质-磷脂膜相互作用提供了独特的机制。在与血液凝固无关的蛋白质中越来越多地发现了Gla结构域。因此，这种膜结合机制在其他生理过程中可能很重要。 [参考：45]

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《Nature structural biology》 |2003年第9期|共6页
作者
Huang MD.; Rigby AC.; Morelli X.; Grant MA.; Huang GQ.; Furie B.; Seaton B.; Furie BC.;
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正文语种 eng
中图分类生物科学;
关键词
Carboxyglutamic acid domain; Blood-coagulation; Factor-ix; Prothrombin fragment-1; Phospholipid-vesicles; Bovine prothrombin; Crystal-structure; Factor-va; Factor-x; Nmr;

机译：羧基谷氨酸结构域;凝血;因子ix;凝血酶原片段-1;磷脂泡;牛凝血酶原;晶体结构;因子va;因子x;Nmr;

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1. Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins [J] . Huang MD., Rigby AC., Morelli X., Nature structural biology . 2003,第9期

机译：维生素K依赖蛋白的Gla结构域结合膜的结构基础
2. Comparison of naturally occurring vitamin K-dependent proteins: correlation of amino acid sequences and membrane binding properties suggests a membrane contact site. [J] . McDonald JF, Shah AM, Schwalbe RA, Biochemistry . 1997,第17期

机译：天然存在的维生素K依赖性蛋白的比较：氨基酸序列与膜结合特性的相关性表明膜接触位点。
3. MULTI-SITE-SPECIFICITY OF THE VITAMIN K-DEPENDENT CARBOXYLASE - IN VITRO CARBOXYLATION OF DES-GAMMA-CARBOXYLATED BONE GLA PROTEIN AND DES-GAMMA-CARBOXYLATED PRO BONE GLA PROTEIN [J] . Benton ME., Suttie JW., Price PA. Biochemistry . 1995,第29期

机译：维生素K依赖性羧化酶的多部位特异性-脱羧羧甲基化的骨GLA蛋白和脱羧羧甲基化的骨GLA蛋白质的体外羧化
4. Structural Feature Extraction Protocol for Classifying Reversible Membrane Binding Protein Domains [C] . Morten Kallberg, Hui Lu Annual International Conference of the IEEE Engineering in Medicine and Biology Society . 2009

机译：用于分类可逆膜结合蛋白域的结构特征提取方案
5. Identification of the membrane contact site and enhanced function of vitamin K-dependent plasma proteins. [D] . Shah, Amit Mahendra. 1997

机译：膜接触部位的鉴定和维生素K依赖性血浆蛋白功能增强。
6. Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein [O] . John D. Kulman, Jeff E. Harris, Ling Xie, 2007

机译：富含脯氨酸的Gla蛋白2是一种细胞表面维生素K依赖性蛋白可与转录共激活因子Yes相关蛋白结合
7. Unique secretion mode of human protein Z : its Gla domain is responsible for inefficient, vitamin K-dependent and warfarin-sensitive secretion [O] . Masayoshi SOURI 2010

机译：人蛋白Z的独特分泌模式：其GLA结构域是负责低效，维生素K依赖性和华法素敏感的分泌物

Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins

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