1tmr: Difference between revisions
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==THE STRUCTURE OF A 19 RESIDUE FRAGMENT FROM THE C-LOOP OF THE FOURTH EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF THROMBOMODULIN== | |||
<StructureSection load='1tmr' size='340' side='right'caption='[[1tmr]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1tmr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TMR FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tmr OCA], [https://pdbe.org/1tmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tmr RCSB], [https://www.ebi.ac.uk/pdbsum/1tmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tmr ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TRBM_HUMAN TRBM_HUMAN] Defects in THBD are the cause of thrombophilia due to thrombomodulin defect (THPH12) [MIM:[https://omim.org/entry/614486 614486]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:7811989</ref> <ref>PMID:9198186</ref> <ref>PMID:12139752</ref> Defects in THBD are a cause of susceptibility to hemolytic uremic syndrome atypical type 6 (AHUS6) [MIM:[https://omim.org/entry/612926 612926]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:19625716</ref> <ref>PMID:20513133</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TRBM_HUMAN TRBM_HUMAN] Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated. | |||
== | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | |||
The solution structure has been determined for a 19-residue peptide that is fully folded at room temperature. The sequence of this peptide is based on the C-loop, residues 371-389, of the fourth epidermal growth factor-like domain of thrombomodulin, a protein that acts as a cofactor for the thrombin activation of protein C. Despite its small size, the peptide forms a compact structure with almost no repeating secondary structure. The results indicate the structure is held together by hydrophobic interactions, which in turn stabilize the two beta-turns in the structure. The first beta-turn in the C-loop represents a conserved motif that is found in the published structures of five other epidermal growth factor-like proteins. The critical role of Phe376 in the stabilization of the first beta-turn is consistent with mutagenesis data with soluble thrombomodulin. The results also show that a small subdomain of a larger protein can fold independently, and therefore it could act as an initiation site for further folding. | The solution structure has been determined for a 19-residue peptide that is fully folded at room temperature. The sequence of this peptide is based on the C-loop, residues 371-389, of the fourth epidermal growth factor-like domain of thrombomodulin, a protein that acts as a cofactor for the thrombin activation of protein C. Despite its small size, the peptide forms a compact structure with almost no repeating secondary structure. The results indicate the structure is held together by hydrophobic interactions, which in turn stabilize the two beta-turns in the structure. The first beta-turn in the C-loop represents a conserved motif that is found in the published structures of five other epidermal growth factor-like proteins. The critical role of Phe376 in the stabilization of the first beta-turn is consistent with mutagenesis data with soluble thrombomodulin. The results also show that a small subdomain of a larger protein can fold independently, and therefore it could act as an initiation site for further folding. | ||
The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin.,Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J J Biol Chem. 1995 Oct 6;270(40):23366-72. PMID:7559494<ref>PMID:7559494</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1tmr" style="background-color:#fffaf0;"></div> | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Adler | [[Category: Adler M]] | ||
[[Category: Light | [[Category: Light DR]] | ||
[[Category: Morser | [[Category: Morser J]] | ||
[[Category: Nitecki | [[Category: Nitecki D]] | ||
[[Category: Seto | [[Category: Seto M]] | ||
