6ayf

From Proteopedia

(Difference between revisions)

Current revision

TRPML3/ML-SA1 complex at pH 7.4

6ayf, resolution 3.62Å

Structural highlights

6ayf is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.62Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

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.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S. A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype. EMBO J. 2008 Apr 23;27(8):1197-205. doi: 10.1038/emboj.2008.56. Epub 2008 Mar 27. PMID:18369318 doi:http://dx.doi.org/10.1038/emboj.2008.56
↑ Martina JA, Lelouvier B, Puertollano R. The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. Traffic. 2009 Aug;10(8):1143-56. Epub 2009 Apr 29. PMID:19497048 doi:http://dx.doi.org/TRA935
↑ Kim HJ, Soyombo AA, Tjon-Kon-Sang S, So I, Muallem S. The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. Traffic. 2009 Aug;10(8):1157-67. doi: 10.1111/j.1600-0854.2009.00924.x. Epub 2009, May 11. PMID:19522758 doi:http://dx.doi.org/10.1111/j.1600-0854.2009.00924.x
↑ Curcio-Morelli C, Zhang P, Venugopal B, Charles FA, Browning MF, Cantiello HF, Slaugenhaupt SA. Functional multimerization of mucolipin channel proteins. J Cell Physiol. 2010 Feb;222(2):328-35. doi: 10.1002/jcp.21956. PMID:19885840 doi:http://dx.doi.org/10.1002/jcp.21956
↑ Lelouvier B, Puertollano R. Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway. J Biol Chem. 2011 Mar 18;286(11):9826-32. doi: 10.1074/jbc.M110.169185. Epub 2011, Jan 18. PMID:21245134 doi:http://dx.doi.org/10.1074/jbc.M110.169185
↑ Guo Z, Grimm C, Becker L, Ricci AJ, Heller S. A novel ion channel formed by interaction of TRPML3 with TRPV5. PLoS One. 2013;8(2):e58174. doi: 10.1371/journal.pone.0058174. Epub 2013 Feb 28. PMID:23469151 doi:http://dx.doi.org/10.1371/journal.pone.0058174
↑ Zhou X, Li M, Su D, Jia Q, Li H, Li X, Yang J. Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states. Nat Struct Mol Biol. 2017 Nov 6. doi: 10.1038/nsmb.3502. PMID:29106414 doi:http://dx.doi.org/10.1038/nsmb.3502

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ayf"

Categories: Homo sapiens | Large Structures | Jia Q | Li H | Li M | Li X | Su D | Yang J | Zhou X

@@ Line 3: / Line 3: @@
 <SX load='6ayf' size='340' side='right' viewer='molstar' caption='[[6ayf]], [[Resolution|resolution]] 3.62&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<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>
-</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>
+</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>
-<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>
+<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>
-<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>
+<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>
 == Function ==
-[[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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Jia, Q]]
+[[Category: Jia Q]]
-[[Category: Li, H]]
+[[Category: Li H]]
-[[Category: Li, M]]
+[[Category: Li M]]
-[[Category: Li, X]]
+[[Category: Li X]]
-[[Category: Su, D]]
+[[Category: Su D]]
-[[Category: Yang, J]]
+[[Category: Yang J]]
-[[Category: Zhou, X]]
+[[Category: Zhou X]]
-[[Category: Ion channel]]
-[[Category: Lysosomal]]
-[[Category: Transport protein]]
-[[Category: Trp channel]]

6ayf

From Proteopedia

Current revision

TRPML3/ML-SA1 complex at pH 7.4

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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