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| - | {{STRUCTURE_3wnx| PDB=3wnx | SCENE= }} | |
| - | ===Crystal structure of ERGIC-53/MCFD2, Calcium/Man3-bound form=== | |
| - | {{ABSTRACT_PUBMED_24498414}} | |
| | | | |
| - | ==Disease== | + | ==Crystal structure of ERGIC-53/MCFD2, Calcium/Man3-bound form== |
| - | [[http://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:[http://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> [[http://www.uniprot.org/uniprot/MCFD2_HUMAN MCFD2_HUMAN]] Defects in MCFD2 are a cause of factor V and factor VIII combined deficiency type 2 (F5F8D2) [MIM:[http://omim.org/entry/613625 613625]]; also known as multiple coagulation factor deficiency 2 (MCFD2). F5F8D2 is a 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:12717434</ref> <ref>PMID:18590741</ref> | + | <StructureSection load='3wnx' size='340' side='right'caption='[[3wnx]], [[Resolution|resolution]] 2.75Å' 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]] 2.75Å</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. |
| | | | |
| - | ==Function==
| + | 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> |
| - | [[http://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> [[http://www.uniprot.org/uniprot/MCFD2_HUMAN MCFD2_HUMAN]] The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. Plays a role in the secretion of coagulation factors.<ref>PMID:12717434</ref>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[3wnx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WNX OCA].
| + | </div> |
| | + | <div class="pdbe-citations 3wnx" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | <ref group="xtra">PMID:024498414</ref><references group="xtra"/><references/>
| + | *[[ERGIC-53|ERGIC-53]] |
| - | [[Category: Kato, K.]] | + | == References == |
| - | [[Category: Satoh, T.]] | + | <references/> |
| - | [[Category: Suzuki, K.]] | + | __TOC__ |
| - | [[Category: Yamaguchi, T.]] | + | </StructureSection> |
| - | [[Category: Beta-sandwich]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Calcium binding]] | + | [[Category: Large Structures]] |
| - | [[Category: Cargo receptor]]
| + | [[Category: Kato K]] |
| - | [[Category: Ef-hand]]
| + | [[Category: Satoh T]] |
| - | [[Category: Er]]
| + | [[Category: Suzuki K]] |
| - | [[Category: Ergic]]
| + | [[Category: Yamaguchi T]] |
| - | [[Category: Protein transport]]
| + | |
| Structural highlights
Disease
LMAN1_HUMAN Defects in LMAN1 are THE cause of factor V and factor VIII combined deficiency type 1 (F5F8D1) [MIM: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.[1]
Function
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.[2] [3]
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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nichols WC, Terry VH, Wheatley MA, Yang A, Zivelin A, Ciavarella N, Stefanile C, Matsushita T, Saito H, de Bosch NB, Ruiz-Saez A, Torres A, Thompson AR, Feinstein DI, White GC, Negrier C, Vinciguerra C, Aktan M, Kaufman RJ, Ginsburg D, Seligsohn U. ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood. 1999 Apr 1;93(7):2261-6. PMID:10090935
- ↑ Nufer O, Kappeler F, Guldbrandsen S, Hauri HP. ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci. 2003 Nov 1;116(Pt 21):4429-40. Epub 2003 Sep 16. PMID:13130098 doi:10.1242/jcs.00759
- ↑ Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet. 2003 Jun;34(2):220-5. PMID:12717434 doi:10.1038/ng1153
- ↑ Satoh T, Suzuki K, Yamaguchi T, Kato K. Structural Basis for Disparate Sugar-Binding Specificities in the Homologous Cargo Receptors ERGIC-53 and VIP36. PLoS One. 2014 Feb 3;9(2):e87963. doi: 10.1371/journal.pone.0087963. eCollection , 2014. PMID:24498414 doi:http://dx.doi.org/10.1371/journal.pone.0087963
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