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| | ==Crystal structure of the carbohydrate recognition domain of LMAN1 in complex with MCFD2== | | ==Crystal structure of the carbohydrate recognition domain of LMAN1 in complex with MCFD2== |
| - | <StructureSection load='3lcp' size='340' side='right' caption='[[3lcp]], [[Resolution|resolution]] 2.45Å' scene=''> | + | <StructureSection load='3lcp' size='340' side='right'caption='[[3lcp]], [[Resolution|resolution]] 2.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lcp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LCP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LCP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lcp]] is a 4 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=3LCP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LCP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.45Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ERGIC53, F5F8D, LMAN1, LMAN1 (AMINO ACIDS 32-277) ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MCFD2, MCFD2 (AMINO ACIDS 58-146), SDNSF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lcp OCA], [http://pdbe.org/3lcp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lcp RCSB], [http://www.ebi.ac.uk/pdbsum/3lcp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lcp ProSAT]</span></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=3lcp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lcp OCA], [https://pdbe.org/3lcp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lcp RCSB], [https://www.ebi.ac.uk/pdbsum/3lcp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lcp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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> | + | [https://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:[https://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> |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bourhis, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Guy, J E]] | + | [[Category: Bourhis JM]] |
| - | [[Category: Kursula, I]] | + | [[Category: Guy JE]] |
| - | [[Category: Lindqvist, Y]] | + | [[Category: Kursula I]] |
| - | [[Category: Wigren, E]] | + | [[Category: Lindqvist Y]] |
| - | [[Category: Calcium]]
| + | [[Category: Wigren E]] |
| - | [[Category: Coagulation factor deficiency]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: Er-golgi transport]]
| + | |
| - | [[Category: Glycoprotein sorting]]
| + | |
| - | [[Category: Golgi apparatus]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Secretory pathway]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transport]]
| + | |
| Structural highlights
Disease
MCFD2_HUMAN Defects in MCFD2 are a cause of factor V and factor VIII combined deficiency type 2 (F5F8D2) [MIM: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.[1] [2]
Function
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.[3]
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 PubMed
LMAN1 is a glycoprotein receptor, mediating transfer from the ER to the ER-Golgi intermediate compartment. Together with the co-receptor MCFD2, it transports coagulation factors V and VIII. Mutations in LMAN1 and MCFD2 can cause combined deficiency of factors V and VIII (F5F8D). We present the crystal structure of the LMAN1/MCFD2 complex and relate it to patient mutations. Circular dichroism data show that the majority of the substitution mutations give rise to a disordered or severely destabilized MCFD2 protein. The few stable mutation variants are found in the binding surface of the complex leading to impaired LMAN1 binding and F5F8D.
Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII.,Wigren E, Bourhis JM, Kursula I, Guy JE, Lindqvist Y FEBS Lett. 2010 Mar 5;584(5):878-82. Epub 2010 Feb 9. PMID:20138881[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ Guy JE, Wigren E, Svard M, Hard T, Lindqvist Y. New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2. J Mol Biol. 2008 Sep 12;381(4):941-55. Epub 2008 Jun 20. PMID:18590741 doi:10.1016/j.jmb.2008.06.042
- ↑ 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
- ↑ Wigren E, Bourhis JM, Kursula I, Guy JE, Lindqvist Y. Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII. FEBS Lett. 2010 Mar 5;584(5):878-82. Epub 2010 Feb 9. PMID:20138881 doi:10.1016/j.febslet.2010.02.009
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