7n70
From Proteopedia
(Difference between revisions)
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==Cryo-EM structure of ATP13A2 in the BeF-bound E2P-like state== | ==Cryo-EM structure of ATP13A2 in the BeF-bound E2P-like state== | ||
| - | <StructureSection load='7n70' size='340' side='right'caption='[[7n70]]' scene=''> | + | <StructureSection load='7n70' size='340' side='right'caption='[[7n70]], [[Resolution|resolution]] 2.80Å' 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=7N70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N70 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7n70]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N70 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=7n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n70 OCA], [https://pdbe.org/7n70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n70 RCSB], [https://www.ebi.ac.uk/pdbsum/7n70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n70 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=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7n70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n70 OCA], [https://pdbe.org/7n70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n70 RCSB], [https://www.ebi.ac.uk/pdbsum/7n70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n70 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 == | ||
| + | Polyamines are small, organic polycations that are ubiquitous and essential to all forms of life. Currently, how polyamines are transported across membranes is not understood. Recent studies have suggested that ATP13A2 and its close homologs, collectively known as P5B-ATPases, are polyamine transporters at endo-/lysosomes. Loss-of-function mutations of ATP13A2 in humans cause hereditary early-onset Parkinson's disease. To understand the polyamine transport mechanism of ATP13A2, we determined high-resolution cryoelectron microscopy (cryo-EM) structures of human ATP13A2 in five distinct conformational intermediates, which together, represent a near-complete transport cycle of ATP13A2. The structural basis of the polyamine specificity was revealed by an endogenous polyamine molecule bound to a narrow, elongated cavity within the transmembrane domain. The structures show an atypical transport path for a water-soluble substrate, in which polyamines may exit within the cytosolic leaflet of the membrane. Our study provides important mechanistic insights into polyamine transport and a framework to understand the functions and mechanisms of P5B-ATPases. | ||
| + | |||
| + | Structural basis of polyamine transport by human ATP13A2 (PARK9).,Sim SI, von Bulow S, Hummer G, Park E Mol Cell. 2021 Oct 21. pii: S1097-2765(21)00684-5. doi:, 10.1016/j.molcel.2021.08.017. PMID:34715013<ref>PMID:34715013</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7n70" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Park E]] | + | [[Category: Park, E]] |
| - | [[Category: Sim | + | [[Category: Sim, S I]] |
| + | [[Category: P-type atpase]] | ||
| + | [[Category: P5b-atpase]] | ||
| + | [[Category: Polyamine transporter]] | ||
| + | [[Category: Transport protein]] | ||
Revision as of 06:29, 1 December 2021
Cryo-EM structure of ATP13A2 in the BeF-bound E2P-like state
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