Thrombomodulin structure and function.

J E Sadler

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PubMed · 9198185

Thrombomodulin structure and function.

J E Sadler

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Abstract

Thrombomodulin is protein cofactor expressed on endothelial cell surfaces that modifies the substrate specificity of thrombin, apparently by an allosteric mechanism. The thrombin-thrombomodulin complex activates protein C, initiating an essential anticoagulant pathway. The cofactor function of membrane-associated thrombomodulin requires the last three of six tandemly repeated EGF-like domains (numbers 4, 5, and 6), as well as a Ser/Thr-rich spacer between EGF-like domain 6 and the transmembrane domain. The Ser/Thr-rich domain is variably modified with a chondroitin sulfate chain that influences the affinity of thrombin binding and the calcium ion dependence of cofactor function. The structure of EGF-like domain 4 has been determined by NMR spectroscopy, and the structure of a complex between thrombin and a peptide from thrombomodulin EGF-like domain 5 was determined by X-ray crystallography. These structures are small steps toward an understanding of how thrombomodulin regulates thrombin.

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Amino Acid Sequence Humans Models, Molecular Molecular Sequence Data Protein Binding Protein C Structure-Activity Relationship Thrombin Thrombomodulin Journal Article Review

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J E Sadler. 1997. Thrombomodulin structure and function.. https://pubmed.ncbi.nlm.nih.gov/9198185/

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