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1tmr

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Revision as of 13:44, 25 December 2019

THE STRUCTURE OF A 19 RESIDUE FRAGMENT FROM THE C-LOOP OF THE FOURTH EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF THROMBOMODULIN

Structural highlights

1tmr is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TRBM_HUMAN] Defects in THBD are the cause of thrombophilia due to thrombomodulin defect (THPH12) [MIM:614486]. A hemostatic disorder characterized by a tendency to thrombosis.^[1] ^[2] ^[3] Defects in THBD are a cause of susceptibility to hemolytic uremic syndrome atypical type 6 (AHUS6) [MIM: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.^[4] ^[5]

Function

[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.

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 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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ohlin AK, Marlar RA. The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease. Blood. 1995 Jan 15;85(2):330-6. PMID:7811989
↑ Ohlin AK, Norlund L, Marlar RA. Thrombomodulin gene variations and thromboembolic disease. Thromb Haemost. 1997 Jul;78(1):396-400. PMID:9198186
↑ Faioni EM, Franchi F, Castaman G, Biguzzi E, Rodeghiero F. Mutations in the thrombomodulin gene are rare in patients with severe thrombophilia. Br J Haematol. 2002 Aug;118(2):595-9. PMID:12139752
↑ Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, Del-Favero J, Plaisance S, Claes B, Lambrechts D, Zoja C, Remuzzi G, Conway EM. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med. 2009 Jul 23;361(4):345-57. doi: 10.1056/NEJMoa0810739. PMID:19625716 doi:10.1056/NEJMoa0810739
↑ Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat. 2010 Jun;31(6):E1445-60. doi: 10.1002/humu.21256. PMID:20513133 doi:10.1002/humu.21256
↑ Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J. The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin. J Biol Chem. 1995 Oct 6;270(40):23366-72. PMID:7559494

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1tmr"

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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]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='1tmr' size='340' side='right'caption='[[1tmr]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1tmr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TMR FirstGlance]. <br>
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Adler, M]]
 [[Category: Light, D R]]

1tmr

From Proteopedia

Revision as of 13:44, 25 December 2019

THE STRUCTURE OF A 19 RESIDUE FRAGMENT FROM THE C-LOOP OF THE FOURTH EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF THROMBOMODULIN

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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