Thrombomodulin: from haemostasis to inflammation and tumourigenesis.
Thrombomodulin (TM), a transmembrane endothelial receptor, participates in coagulation, in inflammation, in cancer and plays a role during embryogenesis. The nucleotide sequence of the TM cDNA allows the structure of this protein to be visualized. The protein starts with a signal peptide, followed by the N-terminal globular domain, six repeats of epidermal growth factor-like sequence, a serine/threonine-rich region, a transmembrane domain and a cytoplasmic domain. High-resolution nuclear magnetic resonance (NMR) spectroscopy was employed to define the exact thrombin-binding region. Residues Y(413)ILDD(417) and D(423)IDE(426) are crucial for binding to thrombin; the two critical amino acids for thrombin binding, Ile(414) and Ile(424), are brought into spatial proximity by beta-sheet structure. There also exist some residues for co-factor activity, namely Asp(349), Glu(357), Tyr(358), Phe(376) and Met(388). The complex transcriptional and post-transcriptional control of TM underline its importance in a wide variety of biological systems and pathophysiological processes.
Koutsi
Aikaterini
A
Department of Biological Chemistry, Medical School, University of Athens, Athens 11527, Greece.
Papapanagiotou
Angeliki
A
Papavassiliou
Athanasios G
AG
D000818:Animals; D005786:Gene Expression Regulation; D006487:Hemostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D013329:Structure-Activity Relationship; D018180:Thrombomodulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D018180:Thrombomodulin