5wj5
From Proteopedia
(Difference between revisions)
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| - | == | + | ==Human TRPML1 channel structure in closed conformation== |
<StructureSection load='5wj5' size='340' side='right' caption='[[5wj5]], [[Resolution|resolution]] 3.70Å' scene=''> | <StructureSection load='5wj5' size='340' side='right' caption='[[5wj5]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
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== 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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:29019983</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5wj5" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 07:02, 25 October 2017
Human TRPML1 channel structure in closed conformation
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