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

@article{Huang2003StructuralBO,
  title={Structural basis of membrane binding by Gla domains of vitamin K–dependent proteins},
  author={Mingdong Huang and Alan C. Rigby and Xavier Morelli and Marianne A. Grant and Guiqing Huang and Bruce Furie and Barbara A. Seaton and Barbara C. Furie},
  journal={Nature Structural Biology},
  year={2003},
  volume={10},
  pages={751-756}
}
In a calcium-dependent interaction critical for blood coagulation, vitamin K–dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via γ-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… 

Computational study of coagulation factor VIIa’s affinity for phospholipid membranes

TLDR
The MD simulation approach provides a structural and dynamic support to the role of P10Q and K32E mutations in the improvement of the membrane contact and a ranking of the rupture force that can be useful in the interpretation of the PS interaction with Gla domains is exhibited.

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TLDR
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TLDR
Protein’C binding to sEPCR and phospholipids is broadly dependent on correct Gla domain folding, but can be selectively influenced by judicious mutation.

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TLDR
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TLDR
Data suggest that, on binding to a membrane surface, prothrombin undergoes a conformational change to a form which binds more tightly to the membrane.

Lipid specificity of the membrane binding domain of coagulation factor X

TLDR
Molecular dynamics simulations were used to develop the first membrane‐bound model of FX‐GLA, and potential PS‐specific binding sites identified.

Tissue factor/factor VIIa complex: role of the membrane surface.

Multifunctional Specificity of the Protein C/Activated Protein C Gla Domain*

TLDR
Results reveal the specific Gla domain residues responsible for mediating protein C/APC molecular recognition with both its cofactor and receptor and further illustrate the multifunctional potential of Gla domains.

The gamma-carboxyglutamic acid domain of anticoagulant protein S is involved in activated protein C cofactor activity, independently of phospholipid binding.

TLDR
By characterizing PS mutants in which PS face 1 and PS face 2 were individually replaced by the corresponding prothrombin faces, it is found that face 1 was necessary for efficient phospholipid binding but that face 2 residues were not strictly required for phospholIPid binding and were involved in the interaction with APC.
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References

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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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