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6ayf

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<SX load='6ayf' size='340' side='right' viewer='molstar' caption='[[6ayf]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
<SX load='6ayf' size='340' side='right' viewer='molstar' caption='[[6ayf]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ayf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AYF FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ayf]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AYF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.62&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCOLN3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<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=6ayf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayf OCA], [http://pdbe.org/6ayf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ayf RCSB], [http://www.ebi.ac.uk/pdbsum/6ayf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayf ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ayf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ayf OCA], [https://pdbe.org/6ayf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ayf RCSB], [https://www.ebi.ac.uk/pdbsum/6ayf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ayf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/MCLN3_HUMAN MCLN3_HUMAN]] Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).[UniProtKB:Q8R4F0]<ref>PMID:18369318</ref> <ref>PMID:19497048</ref> <ref>PMID:19522758</ref> <ref>PMID:19885840</ref> <ref>PMID:21245134</ref> <ref>PMID:23469151</ref>
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[https://www.uniprot.org/uniprot/MCLN3_HUMAN MCLN3_HUMAN] Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).[UniProtKB:Q8R4F0]<ref>PMID:18369318</ref> <ref>PMID:19497048</ref> <ref>PMID:19522758</ref> <ref>PMID:19885840</ref> <ref>PMID:21245134</ref> <ref>PMID:23469151</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 A, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP2 regulate TRPML3 by changing S1 and S2 conformations.
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Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.,Zhou X, Li M, Su D, Jia Q, Li H, Li X, Yang J Nat Struct Mol Biol. 2017 Nov 6. doi: 10.1038/nsmb.3502. PMID:29106414<ref>PMID:29106414</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6ayf" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</SX>
</SX>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Jia, Q]]
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[[Category: Jia Q]]
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[[Category: Li, H]]
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[[Category: Li H]]
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[[Category: Li, M]]
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[[Category: Li M]]
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[[Category: Li, X]]
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[[Category: Li X]]
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[[Category: Su, D]]
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[[Category: Su D]]
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[[Category: Yang, J]]
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[[Category: Yang J]]
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[[Category: Zhou, X]]
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[[Category: Zhou X]]
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[[Category: Ion channel]]
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[[Category: Lysosomal]]
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[[Category: Transport protein]]
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[[Category: Trp channel]]
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Current revision

TRPML3/ML-SA1 complex at pH 7.4

6ayf, resolution 3.62Å

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