7m5v
From Proteopedia
(Difference between revisions)
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| - | == | + | ==human ATP13A2 in the AMPPNP-bound occluded state== |
| - | <StructureSection load='7m5v' size='340' side='right'caption='[[7m5v]]' scene=''> | + | <StructureSection load='7m5v' size='340' side='right'caption='[[7m5v]], [[Resolution|resolution]] 2.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M5V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7m5v]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M5V FirstGlance]. <br> |
| - | </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=7m5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m5v OCA], [https://pdbe.org/7m5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m5v RCSB], [https://www.ebi.ac.uk/pdbsum/7m5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m5v ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1DO:1-DODECANOL'>1DO</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=EUJ:(2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl+dioctanoate'>EUJ</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></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=7m5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m5v OCA], [https://pdbe.org/7m5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m5v RCSB], [https://www.ebi.ac.uk/pdbsum/7m5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m5v ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/AT132_HUMAN AT132_HUMAN]] Autosomal recessive spastic paraplegia type 78;Kufor-Rakeb syndrome;ATP13A2-related juvenile neuronal ceroid lipofuscinosis. The disease is caused by variants affecting the gene represented in this entry. KRS has also been referred to as neuronal ceroid lipofuscinosis 12 (CLN12), due to neuronal and glial lipofuscin deposits detected in the cortex, basal nuclei and cerebellum of some patients.<ref>PMID:22388936</ref> The disease is caused by variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/AT132_HUMAN AT132_HUMAN]] ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (PubMed:31996848). Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (PubMed:31996848). Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (PubMed:22186024). Contributes to cellular zinc homeostasis (PubMed:24603074). Confers cellular protection against Mn(2+) and Zn(2+) toxicity and mitochondrial stress (PubMed:26134396). Required for proper lysosomal and mitochondrial maintenance (PubMed:22296644, PubMed:28137957). Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post-translational levels (PubMed:27278822). Facilitates recruitment of deacetylase HDAC6 to lysosomes to deacetylate CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Promotes secretion of exosomes as well as secretion of SCNA via exosomes (PubMed:25392495, PubMed:24603074). Plays a role in lipid homeostasis (PubMed:31132336).<ref>PMID:22186024</ref> <ref>PMID:22296644</ref> <ref>PMID:24603074</ref> <ref>PMID:25392495</ref> <ref>PMID:26134396</ref> <ref>PMID:27278822</ref> <ref>PMID:28137957</ref> <ref>PMID:30538141</ref> <ref>PMID:31132336</ref> <ref>PMID:31996848</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analog or to spermine in the presence of phosphomimetics determined by cryoelectron microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2's architecture suggests physical principles underlying selective polyamine transport and anticipates a "pump-channel" intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2's potential in neuroprotective therapy. | ||
| + | |||
| + | Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2.,Tillinghast J, Drury S, Bowser D, Benn A, Lee KPK Mol Cell. 2021 Nov 18;81(22):4650-4662.e4. doi: 10.1016/j.molcel.2021.10.002., Epub 2021 Oct 28. PMID:34715014<ref>PMID:34715014</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7m5v" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Lee | + | [[Category: Lee, K P.K]] |
| + | [[Category: Ion transport occluded state]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Transport protein]] | ||
Revision as of 11:49, 27 April 2022
human ATP13A2 in the AMPPNP-bound occluded state
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