2vrg: Difference between revisions
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< | ==Structure of human MCFD2== | ||
<StructureSection load='2vrg' size='340' side='right'caption='[[2vrg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
You may | == Structural highlights == | ||
or the | <table><tr><td colspan='2'>[[2vrg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VRG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VRG FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=2vrg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vrg OCA], [https://pdbe.org/2vrg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vrg RCSB], [https://www.ebi.ac.uk/pdbsum/2vrg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vrg ProSAT]</span></td></tr> | ||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vr/2vrg_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vrg ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human MCFD2 (multiple coagulation factor deficiency 2) is a 16-kDa protein known to participate in transport of the glycosylated human coagulation factors V and VIII along the secretory pathway. Mutations in MCFD2 or in its binding partner, the membrane-bound transporter ERGIC (endoplasmic reticulum-Golgi intermediate compartment)-53, cause a mild form of inherited hemophilia known as combined deficiency of factors V and VIII (F5F8D). While ERGIC-53 is known to be a lectin-type mannose binding protein, the role of MCFD2 in the secretory pathway is comparatively unclear. MCFD2 has been shown to bind both ERGIC-53 and the blood coagulation factors, but little is known about the binding sites or the true function of the protein. In order to facilitate understanding of the function of MCFD2 and the mechanism by which mutations in the protein cause F5F8D, we have determined the structure of human MCFD2 in solution by NMR. Our results show the folding of MCFD2 to be dependent on availability of calcium ions. The protein, which is disordered in the apo state, folds upon binding of Ca(2+) to the two EF-hand motifs of its C-terminus, while retaining some localized disorder in the N-terminus. NMR studies on two disease-causing mutant variants of MCFD2 show both to be predominantly disordered, even in the presence of calcium ions. These results provide an explanation for the previously observed calcium dependence of the MCFD2-ERGIC-53 interaction and, furthermore, clarify the means by which mutations in this protein result in inefficient secretion of blood coagulation factors V and VIII. | |||
New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2.,Guy JE, Wigren E, Svard M, Hard T, Lindqvist Y J Mol Biol. 2008 Sep 12;381(4):941-55. Epub 2008 Jun 20. PMID:18590741<ref>PMID:18590741</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vrg" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Guy, J E]] | |||
== | [[Category: Hard, T]] | ||
< | [[Category: Lindqvist, Y]] | ||
[[Category: | [[Category: Svard, M]] | ||
[[Category: Guy, J E | [[Category: Wigren, E]] | ||
[[Category: Hard, T | |||
[[Category: Lindqvist, Y | |||
[[Category: Svard, M | |||
[[Category: Wigren, E | |||
[[Category: Calcium]] | [[Category: Calcium]] | ||
[[Category: Coagulation factor deficiency]] | [[Category: Coagulation factor deficiency]] | ||
| Line 42: | Line 49: | ||
[[Category: Secretory pathway]] | [[Category: Secretory pathway]] | ||
[[Category: Transport]] | [[Category: Transport]] | ||
Latest revision as of 00:01, 21 October 2021
Structure of human MCFD2Structure of human MCFD2
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman MCFD2 (multiple coagulation factor deficiency 2) is a 16-kDa protein known to participate in transport of the glycosylated human coagulation factors V and VIII along the secretory pathway. Mutations in MCFD2 or in its binding partner, the membrane-bound transporter ERGIC (endoplasmic reticulum-Golgi intermediate compartment)-53, cause a mild form of inherited hemophilia known as combined deficiency of factors V and VIII (F5F8D). While ERGIC-53 is known to be a lectin-type mannose binding protein, the role of MCFD2 in the secretory pathway is comparatively unclear. MCFD2 has been shown to bind both ERGIC-53 and the blood coagulation factors, but little is known about the binding sites or the true function of the protein. In order to facilitate understanding of the function of MCFD2 and the mechanism by which mutations in the protein cause F5F8D, we have determined the structure of human MCFD2 in solution by NMR. Our results show the folding of MCFD2 to be dependent on availability of calcium ions. The protein, which is disordered in the apo state, folds upon binding of Ca(2+) to the two EF-hand motifs of its C-terminus, while retaining some localized disorder in the N-terminus. NMR studies on two disease-causing mutant variants of MCFD2 show both to be predominantly disordered, even in the presence of calcium ions. These results provide an explanation for the previously observed calcium dependence of the MCFD2-ERGIC-53 interaction and, furthermore, clarify the means by which mutations in this protein result in inefficient secretion of blood coagulation factors V and VIII. New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2.,Guy JE, Wigren E, Svard M, Hard T, Lindqvist Y J Mol Biol. 2008 Sep 12;381(4):941-55. Epub 2008 Jun 20. PMID:18590741[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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