5nnj
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='5nnj' size='340' side='right' caption='[[5nnj]], [[Resolution|resolution]] 4.00Å' scene=''> | <StructureSection load='5nnj' size='340' side='right' caption='[[5nnj]], [[Resolution|resolution]] 4.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5nnj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NNJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nnj]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NNJ 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></td></tr> | </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></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sort1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5nnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nnj OCA], [http://pdbe.org/5nnj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nnj RCSB], [http://www.ebi.ac.uk/pdbsum/5nnj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nnj 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=5nnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nnj OCA], [http://pdbe.org/5nnj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nnj RCSB], [http://www.ebi.ac.uk/pdbsum/5nnj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nnj ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SORT_MOUSE SORT_MOUSE]] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.<ref>PMID:10594043</ref> <ref>PMID:15236332</ref> <ref>PMID:15236333</ref> <ref>PMID:15372498</ref> <ref>PMID:15992544</ref> <ref>PMID:19407813</ref> <ref>PMID:21102451</ref> | [[http://www.uniprot.org/uniprot/SORT_MOUSE SORT_MOUSE]] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.<ref>PMID:10594043</ref> <ref>PMID:15236332</ref> <ref>PMID:15236333</ref> <ref>PMID:15372498</ref> <ref>PMID:15992544</ref> <ref>PMID:19407813</ref> <ref>PMID:21102451</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a beta-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors. | ||
| + | |||
| + | Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release.,Leloup N, Lossl P, Meijer DH, Brennich M, Heck AJR, Thies-Weesie DME, Janssen BJC Nat Commun. 2017 Nov 22;8(1):1708. doi: 10.1038/s41467-017-01485-5. PMID:29167428<ref>PMID:29167428</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5nnj" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Lk3 transgenic mice]] | ||
[[Category: Janssen, B J.C]] | [[Category: Janssen, B J.C]] | ||
[[Category: Leloup, N O.L]] | [[Category: Leloup, N O.L]] | ||
Revision as of 07:43, 6 December 2017
Dimer structure of Sortilin ectodomain crystal form 3, 4.0 Angstrom
| |||||||||||
