6nq0: Difference between revisions

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'''Unreleased structure'''


The entry 6nq0 is ON HOLD
==Cryo-EM structure of human TPC2 channel in the ligand-bound open state==
<SX load='6nq0' size='340' side='right' viewer='molstar' caption='[[6nq0]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nq0]] is a 2 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=6NQ0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NQ0 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></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TPCN2, TPC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6nq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nq0 OCA], [http://pdbe.org/6nq0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nq0 RCSB], [http://www.ebi.ac.uk/pdbsum/6nq0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nq0 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TPC2_HUMAN TPC2_HUMAN]] Nicotinic acid adenine dinucleotide phosphate (NAADP) receptor that may function as one of the major voltage-gated Ca(2+) channels (VDCC) across the lysosomal membrane. May be involved in smooth muscle contraction.<ref>PMID:19387438</ref> <ref>PMID:19620632</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-activated, Na(+) selective channel, in the ligand-bound and apo states. The apo structure captures the closed conformation, while the ligand-bound form features the channel in both open and closed conformations. Combined with functional analysis, these structures provide insights into the mechanism of PI(3,5)P2-regulated gating of TPC2, which is distinct from that of TPC1. Specifically, the endolysosome-specific PI(3,5)P2 binds at the first 6-TM and activates the channel - independently of the membrane potential - by inducing a structural change at the pore-lining inner helix (IS6), which forms a continuous helix in the open state but breaks into two segments at Gly317 in the closed state. Additionally, structural comparison to the voltage-dependent TPC1 structure allowed us to identify Ile551 as being responsible for the loss of voltage dependence in TPC2.


Authors: She, J., Zeng, W.Z., Guo, J.T., Chen, Q.F., Bai, X.C., Jiang, Y.X.
Structural mechanisms of phospholipid activation of the human TPC2 channel.,She J, Zeng W, Guo J, Chen Q, Bai XC, Jiang Y Elife. 2019 Mar 12;8. pii: 45222. doi: 10.7554/eLife.45222. PMID:30860481<ref>PMID:30860481</ref>


Description: Cryo-EM structure of human TPC2 channel in the ligand-bound open state
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6nq0" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Bai, X]]
[[Category: Chen, Q]]
[[Category: Guo, J]]
[[Category: Jiang, Y]]
[[Category: She, J]]
[[Category: She, J]]
[[Category: Jiang, Y.X]]
[[Category: Zeng, W]]
[[Category: Bai, X.C]]
[[Category: Channel]]
[[Category: Chen, Q.F]]
[[Category: Lysosome]]
[[Category: Zeng, W.Z]]
[[Category: Transport protein]]
[[Category: Guo, J.T]]

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