3a4u: Difference between revisions
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== | ==Crystal structure of MCFD2 in complex with carbohydrate recognition domain of ERGIC-53== | ||
[[http://www.uniprot.org/uniprot/LMAN1_HUMAN LMAN1_HUMAN | <StructureSection load='3a4u' size='340' side='right'caption='[[3a4u]], [[Resolution|resolution]] 1.84Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3a4u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3A4U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3A4U FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.84Å</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>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=3a4u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3a4u OCA], [https://pdbe.org/3a4u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3a4u RCSB], [https://www.ebi.ac.uk/pdbsum/3a4u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3a4u ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/LMAN1_HUMAN LMAN1_HUMAN] Defects in LMAN1 are THE cause of factor V and factor VIII combined deficiency type 1 (F5F8D1) [MIM:[https://omim.org/entry/227300 227300]; also known as multiple coagulation factor deficiency I (MCFD1). F5F8D1 is an autosomal recessive blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.<ref>PMID:10090935</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LMAN1_HUMAN LMAN1_HUMAN] Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins.<ref>PMID:13130098</ref> <ref>PMID:12717434</ref> | |||
== 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/a4/3a4u_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3a4u ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Combined deficiency of coagulation factors V and VIII (F5F8D), an autosomal recessive disorder characterized by coordinate reduction in the plasma levels of factor V (FV) and factor VIII (FVIII), is genetically linked to mutations in the transmembrane lectin ERGIC-53 and the soluble calcium-binding protein MCFD2. Growing evidence indicates that these two proteins form a complex recycling between the endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment and thereby function as a cargo receptor in the early secretory pathway of FV and FVIII. For better understanding of the mechanisms underlying the functional coordination of ERGIC-53 and MCFD2, we herein characterize their interaction by x-ray crystallographic analysis in conjunction with NMR and ultracentrifugation analyses. Inspection of the combined data reveals that ERGIC-53-CRD binds MCFD2 through its molecular surface remote from the sugar-binding site, giving rise to a 11 complex in solution. The interaction is independent of sugar-binding of ERGIC-53 and involves most of the missense mutation sites of MCFD2 so far reported in F5F8D. Comparison with the previously reported uncomplexed structure of each protein indicates that MCFD2 but not ERGIC-53-CRD undergoes significant conformational alterations upon complex formation. Our findings provide a structural basis for the cooperative interplay between ERGIC-53 and MCFD2 in capturing FV and FVIII. | |||
Structural basis for the cooperative interplay between the two causative gene products of combined factor V and factor VIII deficiency.,Nishio M, Kamiya Y, Mizushima T, Wakatsuki S, Sasakawa H, Yamamoto K, Uchiyama S, Noda M, McKay AR, Fukui K, Hauri HP, Kato K Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4034-9. Epub 2010 Feb 8. PMID:20142513<ref>PMID:20142513</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3a4u" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[ERGIC-53|ERGIC-53]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Fukui | [[Category: Large Structures]] | ||
[[Category: Hauri | [[Category: Fukui K]] | ||
[[Category: Kamiya | [[Category: Hauri HP]] | ||
[[Category: Kato | [[Category: Kamiya Y]] | ||
[[Category: McKay | [[Category: Kato K]] | ||
[[Category: Mizushima | [[Category: McKay AR]] | ||
[[Category: Nishio | [[Category: Mizushima T]] | ||
[[Category: Noda | [[Category: Nishio M]] | ||
[[Category: Sasakawa | [[Category: Noda M]] | ||
[[Category: Uchiyama | [[Category: Sasakawa H]] | ||
[[Category: Wakatsuki | [[Category: Uchiyama S]] | ||
[[Category: Yamamoto | [[Category: Wakatsuki S]] | ||
[[Category: Yamamoto K]] | |||