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| | ==Human TRPML1 channel structure in closed conformation== | | ==Human TRPML1 channel structure in closed conformation== |
| - | <SX load='5wj5' size='340' side='right' viewer='molstar' caption='[[5wj5]], [[Resolution|resolution]] 3.70Å' scene=''> | + | <SX load='5wj5' size='340' side='right' viewer='molstar' caption='[[5wj5]], [[Resolution|resolution]] 3.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wj5]] 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=5WJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WJ5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wj5]] 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=5WJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WJ5 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MCOLN1, ML4, MSTP080 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 3.72Å</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=5wj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wj5 OCA], [http://pdbe.org/5wj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wj5 RCSB], [http://www.ebi.ac.uk/pdbsum/5wj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wj5 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=5wj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wj5 OCA], [https://pdbe.org/5wj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wj5 RCSB], [https://www.ebi.ac.uk/pdbsum/5wj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wj5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN]] Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN] Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN]] Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.<ref>PMID:12459486</ref> <ref>PMID:14749347</ref> | + | [https://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN] Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.<ref>PMID:12459486</ref> <ref>PMID:14749347</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Schmiege, P]] | + | [[Category: Schmiege P]] |
| - | [[Category: Human trpml1]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Disease
MCLN1_HUMAN Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry.
Function
MCLN1_HUMAN Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.[1] [2]
Publication Abstract from PubMed
Transient receptor potential mucolipin 1 (TRPML1) is a Ca2+-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-A apo structure at pH 7.0 in the closed state, and a 3.49-A agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily. The opening of TRPML1 is associated with distinct dilations of its lower gate together with a slight structural movement of pore helix 1. Our work reveals the regulatory mechanism of TRPML channels, facilitates better understanding of TRP channel activation, and provides insights into the molecular basis of mucolipidosis type IV pathogenesis.
Human TRPML1 channel structures in open and closed conformations.,Schmiege P, Fine M, Blobel G, Li X Nature. 2017 Oct 19;550(7676):366-370. doi: 10.1038/nature24036. Epub 2017 Oct, 11. PMID:29019983[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ LaPlante JM, Falardeau J, Sun M, Kanazirska M, Brown EM, Slaugenhaupt SA, Vassilev PM. Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway. FEBS Lett. 2002 Dec 4;532(1-2):183-7. PMID:12459486
- ↑ Raychowdhury MK, Gonzalez-Perrett S, Montalbetti N, Timpanaro GA, Chasan B, Goldmann WH, Stahl S, Cooney A, Goldin E, Cantiello HF. Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel. Hum Mol Genet. 2004 Mar 15;13(6):617-27. Epub 2004 Jan 28. PMID:14749347 doi:http://dx.doi.org/10.1093/hmg/ddh067
- ↑ Schmiege P, Fine M, Blobel G, Li X. Human TRPML1 channel structures in open and closed conformations. Nature. 2017 Oct 19;550(7676):366-370. doi: 10.1038/nature24036. Epub 2017 Oct, 11. PMID:29019983 doi:http://dx.doi.org/10.1038/nature24036
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