View source for 3wnx


==Crystal structure of ERGIC-53/MCFD2, Calcium/Man3-bound form==
<StructureSection load='3wnx' size='340' side='right'caption='[[3wnx]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3wnx]] 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=3WNX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WNX 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]] 2.75&#8491;</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=PRD_900111:2alpha-alpha-mannobiose'>PRD_900111</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=3wnx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wnx OCA], [https://pdbe.org/3wnx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wnx RCSB], [https://www.ebi.ac.uk/pdbsum/3wnx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wnx 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ERGIC-53 and VIP36 are categorized as leguminous type (L-type) lectins, and they function as cargo receptors for trafficking certain N-linked glycoproteins in the secretory pathway in animal cells. They share structural similarities in their carbohydrate recognition domains (CRDs) but exhibit distinct sugar-binding specificities and affinities. VIP36 specifically interacts with the alpha1,2-linked D1 mannosyl arm without terminal glucosylation, while ERGIC-53 shows a broader specificity and lower binding affinity to the high-mannose-type oligosaccharides, irrespective of the presence or absence of the non-reducing terminal glucose residue at the D1 arm. In this study, we determined the crystal structure of ERGIC-53-CRD in complex with their binding partner, MCFD2 and the alpha1,2 mannotriose which corresponds to the trisaccharide of the D1 arm of high-mannose-type glycans. ERGIC-53 can interact with the D1 trimannosyl arm in two alternative modes, one of which is similar but distinct from that previously observed for VIP36. ERGIC-53 has a shallower sugar-binding pocket than VIP36 because of the single amino acid substitution, Asp-to-Gly. This enables ERGIC-53 to accommodate the non-reducing terminal glucose of the D1 arm in its CRD. In the other interaction mode, the 3-OH group of the terminal mannose was situated outward with respect to the sugar binding pocket, also enabling the Glcalpha1-3 linkage formation without steric hindrance. Our findings thus provide a structural basis for the broad sugar-binding specificity of the ERGIC-53/MCFD2 cargo receptor complex.

Structural Basis for Disparate Sugar-Binding Specificities in the Homologous Cargo Receptors ERGIC-53 and VIP36.,Satoh T, Suzuki K, Yamaguchi T, Kato K PLoS One. 2014 Feb 3;9(2):e87963. doi: 10.1371/journal.pone.0087963. eCollection , 2014. PMID:24498414<ref>PMID:24498414</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3wnx" style="background-color:#fffaf0;"></div>

==See Also==
*[[ERGIC-53|ERGIC-53]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kato K]]
[[Category: Satoh T]]
[[Category: Suzuki K]]
[[Category: Yamaguchi T]]