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| | <StructureSection load='5tjc' size='340' side='right'caption='[[5tjc]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='5tjc' size='340' side='right'caption='[[5tjc]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tjc]] is a 1 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=5TJC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TJC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tjc]] is a 1 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=5TJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TJC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tjb|5tjb]], [[5tja|5tja]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tjc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjc OCA], [https://pdbe.org/5tjc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tjc RCSB], [https://www.ebi.ac.uk/pdbsum/5tjc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjc ProSAT]</span></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=5tjc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjc OCA], [http://pdbe.org/5tjc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tjc RCSB], [http://www.ebi.ac.uk/pdbsum/5tjc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjc 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__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Benvin, N M]] | + | [[Category: Benvin NM]] |
| - | [[Category: Li, H]] | + | [[Category: Li H]] |
| - | [[Category: Li, M]] | + | [[Category: Li M]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Michailidis, I E]] | + | [[Category: Michailidis IE]] |
| - | [[Category: Su, D]] | + | [[Category: Su D]] |
| - | [[Category: Tong, L]] | + | [[Category: Tong L]] |
| - | [[Category: Wang, S]] | + | [[Category: Wang S]] |
| - | [[Category: Yang, J]] | + | [[Category: Yang J]] |
| - | [[Category: Zhang, W K]] | + | [[Category: Zhang WK]] |
| - | [[Category: Zhou, X]] | + | [[Category: Zhou X]] |
| - | [[Category: Calcium and ph regulation]]
| + | |
| - | [[Category: Endolysosomal lumen]]
| + | |
| - | [[Category: Tetramer]]
| + | |
| - | [[Category: Transport 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
The activities of organellar ion channels are often regulated by Ca2+ and H+, which are present in high concentrations in many organelles. Here we report a structural element critical for dual Ca2+/pH regulation of TRPML1, a Ca2+-release channel crucial for endolysosomal function. TRPML1 mutations cause mucolipidosis type IV (MLIV), a severe lysosomal storage disorder characterized by neurodegeneration, mental retardation and blindness. We obtained crystal structures of the 213-residue luminal domain of human TRPML1 containing three missense MLIV-causing mutations. This domain forms a tetramer with a highly electronegative central pore formed by a novel luminal pore loop. Cysteine cross-linking and cryo-EM analyses confirmed that this architecture occurs in the full-length channel. Structure-function studies demonstrated that Ca2+ and H+ interact with the luminal pore and exert physiologically important regulation. The MLIV-causing mutations disrupt the luminal-domain structure and cause TRPML1 mislocalization. Our study reveals the structural underpinnings of TRPML1's regulation, assembly and pathogenesis.
Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel.,Li M, Zhang WK, Benvin NM, Zhou X, Su D, Li H, Wang S, Michailidis IE, Tong L, Li X, Yang J Nat Struct Mol Biol. 2017 Mar;24(3):205-213. doi: 10.1038/nsmb.3362. Epub 2017, Jan 23. PMID:28112729[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
- ↑ Li M, Zhang WK, Benvin NM, Zhou X, Su D, Li H, Wang S, Michailidis IE, Tong L, Li X, Yang J. Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel. Nat Struct Mol Biol. 2017 Mar;24(3):205-213. doi: 10.1038/nsmb.3362. Epub 2017, Jan 23. PMID:28112729 doi:http://dx.doi.org/10.1038/nsmb.3362
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