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| | <SX load='6c9a' size='340' side='right' viewer='molstar' caption='[[6c9a]], [[Resolution|resolution]] 3.20Å' scene=''> | | <SX load='6c9a' size='340' side='right' viewer='molstar' caption='[[6c9a]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6c9a]] is a 2 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=6C9A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6C9A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6c9a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6C9A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6c96|6c96]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tpcn1, Kiaa1169, Tpc1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6c9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c9a OCA], [https://pdbe.org/6c9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6c9a RCSB], [https://www.ebi.ac.uk/pdbsum/6c9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6c9a ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6c9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c9a OCA], [http://pdbe.org/6c9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c9a RCSB], [http://www.ebi.ac.uk/pdbsum/6c9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c9a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TPC1_MOUSE TPC1_MOUSE]] Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal and endosomal membrane. | + | [https://www.uniprot.org/uniprot/TPC1_MOUSE TPC1_MOUSE] Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal and endosomal membrane. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bai, X]] | + | [[Category: Bai X]] |
| - | [[Category: Chen, Q]] | + | [[Category: Chen Q]] |
| - | [[Category: Guo, J]] | + | [[Category: Guo J]] |
| - | [[Category: Jiang, Y]] | + | [[Category: Jiang Y]] |
| - | [[Category: She, J]] | + | [[Category: She J]] |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
TPC1_MOUSE Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal and endosomal membrane.
Publication Abstract from PubMed
The organellar two-pore channel (TPC) functions as a homodimer, in which each subunit contains two homologous Shaker-like six-transmembrane (6-TM)-domain repeats. TPCs belong to the voltage-gated ion channel superfamily and are ubiquitously expressed in animals and plants. Mammalian TPC1 and TPC2 are localized at the endolysosomal membrane, and have critical roles in regulating the physiological functions of these acidic organelles. Here we present electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)-activated Na(+)-selective channel-in both the apo closed state and ligand-bound open state. Combined with functional analysis, these structures provide comprehensive structural insights into the selectivity and gating mechanisms of mammalian TPC channels. The channel has a coin-slot-shaped ion pathway in the filter that defines the selectivity of mammalian TPCs. Only the voltage-sensing domain from the second 6-TM domain confers voltage dependence on MmTPC1. Endolysosome-specific PtdIns(3,5)P2 binds to the first 6-TM domain and activates the channel under conditions of depolarizing membrane potential. Structural comparisons between the apo and PtdIns(3,5)P2-bound structures show the interplay between voltage and ligand in channel activation. These MmTPC1 structures reveal lipid binding and regulation in a 6-TM voltage-gated channel, which is of interest in light of the emerging recognition of the importance of phosphoinositide regulation of ion channels.
Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.,She J, Guo J, Chen Q, Zeng W, Jiang Y, Bai XC Nature. 2018 Mar 21. pii: nature26139. doi: 10.1038/nature26139. PMID:29562233[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ She J, Guo J, Chen Q, Zeng W, Jiang Y, Bai XC. Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel. Nature. 2018 Mar 21. pii: nature26139. doi: 10.1038/nature26139. PMID:29562233 doi:http://dx.doi.org/10.1038/nature26139
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