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| | ==Structural insights of TM domain of LAMP-2A in DPC micelles== | | ==Structural insights of TM domain of LAMP-2A in DPC micelles== |
| - | <StructureSection load='2mom' size='340' side='right' caption='[[2mom]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mom' size='340' side='right'caption='[[2mom]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mom]] is a 3 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MOM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mom]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MOM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MOM FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mof|2mof]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mom OCA], [http://pdbe.org/2mom PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mom RCSB], [http://www.ebi.ac.uk/pdbsum/2mom PDBsum]</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=2mom FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mom OCA], [https://pdbe.org/2mom PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mom RCSB], [https://www.ebi.ac.uk/pdbsum/2mom PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mom ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/LAMP2_HUMAN LAMP2_HUMAN]] Glycogen storage disease due to LAMP-2 deficiency. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/LAMP2_HUMAN LAMP2_HUMAN] Glycogen storage disease due to LAMP-2 deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LAMP2_HUMAN LAMP2_HUMAN]] Implicated in tumor cell metastasis. May function in protection of the lysosomal membrane from autodigestion, maintenance of the acidic environment of the lysosome, adhesion when expressed on the cell surface (plasma membrane), and inter- and intracellular signal transduction. Protects cells from the toxic effects of methylating mutagens.<ref>PMID:8407947</ref> | + | [https://www.uniprot.org/uniprot/LAMP2_HUMAN LAMP2_HUMAN] Implicated in tumor cell metastasis. May function in protection of the lysosomal membrane from autodigestion, maintenance of the acidic environment of the lysosome, adhesion when expressed on the cell surface (plasma membrane), and inter- and intracellular signal transduction. Protects cells from the toxic effects of methylating mutagens.<ref>PMID:8407947</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Chaperone-mediated autophagy (CMA) is a highly regulated cellular process that mediates the degradation of a selective subset of cytosolic proteins in lysosomes. Increasing CMA activity is one way for a cell to respond to stress, and it leads to enhanced turnover of non-critical cytosolic proteins into sources of energy or clearance of unwanted or damaged proteins from the cytosol. The lysosome-associated membrane protein type 2a (LAMP-2A) together with a complex of chaperones and co-chaperones are key regulators of CMA. LAMP-2A is a transmembrane protein component for protein translocation to the lysosome. Here we present a study of the structure and dynamics of the transmembrane domain of human LAMP-2A in n-dodecylphosphocholine micelles by nuclear magnetic resonance (NMR). We showed that LAMP-2A exists as a homotrimer in which the membrane-spanning helices wrap around each other to form a parallel coiled coil conformation, whereas its cytosolic tail is flexible and exposed to the cytosol. This cytosolic tail of LAMP-2A interacts with chaperone Hsc70 and a CMA substrate RNase A with comparable affinity but not with Hsp40 and RNase S peptide. Because the substrates and the chaperone complex can bind at the same time, thus creating a bimodal interaction, we propose that substrate recognition by chaperones and targeting to the lysosomal membrane by LAMP-2A are coupled. This can increase substrate affinity and specificity as well as prevent substrate aggregation, assist in the unfolding of the substrate, and promote the formation of the higher order complex of LAMP-2A required for translocation.
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| - | Structure of Transmembrane Domain of Lysosome-associated Membrane Protein Type 2a (LAMP-2A) Reveals Key Features for Substrate Specificity in Chaperone-mediated Autophagy.,Rout AK, Strub MP, Piszczek G, Tjandra N J Biol Chem. 2014 Dec 19;289(51):35111-23. doi: 10.1074/jbc.M114.609446. Epub, 2014 Oct 22. PMID:25342746<ref>PMID:25342746</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 2mom" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Rout, A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Tjandra, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Membrane protein]] | + | [[Category: Rout A]] |
| - | [[Category: Protein]] | + | [[Category: Tjandra N]] |
