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| | ==Structure of the lysosomal domain of limp-2== | | ==Structure of the lysosomal domain of limp-2== |
| - | <StructureSection load='4f7b' size='340' side='right' caption='[[4f7b]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4f7b' size='340' side='right'caption='[[4f7b]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4f7b]] is a 6 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=4F7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4F7B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4f7b]] is a 6 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=4F7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4F7B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD36L2, LIMPII, SCARB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4f7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7b OCA], [https://pdbe.org/4f7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4f7b RCSB], [https://www.ebi.ac.uk/pdbsum/4f7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7b ProSAT]</span></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=4f7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f7b OCA], [http://pdbe.org/4f7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4f7b RCSB], [http://www.ebi.ac.uk/pdbsum/4f7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4f7b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SCRB2_HUMAN SCRB2_HUMAN]] Unverricht-Lundborg disease;Gaucher disease type 1;Action myoclonus - renal failure syndrome. The disease is caused by mutations affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease. | + | [https://www.uniprot.org/uniprot/SCRB2_HUMAN SCRB2_HUMAN] Unverricht-Lundborg disease;Gaucher disease type 1;Action myoclonus - renal failure syndrome. The disease is caused by mutations affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SCRB2_HUMAN SCRB2_HUMAN]] Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.<ref>PMID:18022370</ref> | + | [https://www.uniprot.org/uniprot/SCRB2_HUMAN SCRB2_HUMAN] Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.<ref>PMID:18022370</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Bountra, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Dhe-Paganon, D]] | + | [[Category: Bountra C]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Dhe-Paganon D]] |
| - | [[Category: Neculai, D]] | + | [[Category: Edwards AM]] |
| - | [[Category: Neculai, M]] | + | [[Category: Neculai D]] |
| - | [[Category: Pizzaro, J C]] | + | [[Category: Neculai M]] |
| - | [[Category: Ravichandran, M]] | + | [[Category: Pizzaro JC]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Ravichandran M]] |
| - | [[Category: Seitova, A]] | + | [[Category: Seitova A]] |
| - | [[Category: Atherosclerosis]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Lipid transport]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Scavenger receptor]]
| + | |
| - | [[Category: Sgc]]
| + | |
| Structural highlights
Disease
SCRB2_HUMAN Unverricht-Lundborg disease;Gaucher disease type 1;Action myoclonus - renal failure syndrome. The disease is caused by mutations affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease.
Function
SCRB2_HUMAN Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.[1]
Publication Abstract from PubMed
Members of the CD36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. They recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. The family consists of three members: SR-BI (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis C virus), LIMP-2/LGP85 (which mediates lysosomal delivery of beta-glucocerebrosidase and serves as a receptor for enterovirus 71 and coxsackieviruses) and CD36 (a fatty-acid transporter and receptor for phagocytosis of effete cells and Plasmodium-infected erythrocytes). Notably, CD36 is also a receptor for modified lipoproteins and beta-amyloid, and has been implicated in the pathogenesis of atherosclerosis and of Alzheimer's disease. Despite their prominent roles in health and disease, understanding the function and abnormalities of the CD36 family members has been hampered by the paucity of information about their structure. Here we determine the crystal structure of LIMP-2 and infer, by homology modelling, the structure of SR-BI and CD36. LIMP-2 shows a helical bundle where beta-glucocerebrosidase binds, and where ligands are most likely to bind to SR-BI and CD36. Remarkably, the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SR-BI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. We provide evidence supporting a model whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel, accounting for the selective lipid transfer characteristic of SR-BI and CD36.
Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36.,Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S Nature. 2013 Oct 27. doi: 10.1038/nature12684. PMID:24162852[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, Brondyk W, Van Patten S, Edmunds T, Saftig P. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007 Nov 16;131(4):770-83. PMID:18022370 doi:http://dx.doi.org/10.1016/j.cell.2007.10.018
- ↑ Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S. Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature. 2013 Oct 27. doi: 10.1038/nature12684. PMID:24162852 doi:http://dx.doi.org/10.1038/nature12684
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