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4f7b

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Revision as of 17:05, 11 August 2016

Structure of the lysosomal domain of limp-2

Structural highlights

4f7b is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Gene:	CD36L2, LIMPII, SCARB2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4f7b"

@@ Line 1: / Line 1: @@
 ==Structure of the lysosomal domain of limp-2==
 <StructureSection load='4f7b' size='340' side='right' caption='[[4f7b]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </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>
 <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'>[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://www.rcsb.org/pdb/explore.do?structureId=4f7b RCSB], [http://www.ebi.ac.uk/pdbsum/4f7b PDBsum]</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>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4f7b" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4f7b

From Proteopedia

Revision as of 17:05, 11 August 2016

Structure of the lysosomal domain of limp-2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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