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6OY3

nhTMEM16 L302A +Ca2+ in nanodiscs

Summary for 6OY3
Entry DOI10.2210/pdb6oy3/pdb
EMDB information20221
DescriptornhTMEM16, CALCIUM ION (2 entities in total)
Functional Keywordstmem16, scramblase, lipid transport, anoactamin
Biological sourceNectria haematococca (strain 77-13-4 / ATCC MYA-4622 / FGSC 9596 / MPVI)
Total number of polymer chains2
Total formula weight166476.17
Authors
Falzone, M.,Lee, B.C.,Accardi, A. (deposition date: 2019-05-14, release date: 2019-11-06, Last modification date: 2024-03-20)
Primary citationKhelashvili, G.,Falzone, M.E.,Cheng, X.,Lee, B.C.,Accardi, A.,Weinstein, H.
Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca 2+ -bound nhTMEM16.
Nat Commun, 10:4972-4972, 2019
Cited by
PubMed Abstract: Both lipid and ion translocation by Ca-regulated TMEM16 transmembrane proteins utilizes a membrane-exposed hydrophilic groove. Several conformations of the groove are observed in TMEM16 protein structures, but how these conformations form, and what functions they support, remains unknown. From analyses of atomistic molecular dynamics simulations of Ca-bound nhTMEM16 we find that the mechanism of a conformational transition of the groove from membrane-exposed to occluded from the membrane involves the repositioning of transmembrane helix 4 (TM4) following its disengagement from a TM3/TM4 interaction interface. Residue L302 is a key element in the hydrophobic TM3/TM4 interaction patch that braces the open-groove conformation, which should be changed by an L302A mutation. The structure of the L302A mutant determined by cryogenic electron microscopy (cryo-EM) reveals a partially closed groove that could translocate ions, but not lipids. This is corroborated with functional assays showing severely impaired lipid scrambling, but robust channel activity by L302A.
PubMed: 31672969
DOI: 10.1038/s41467-019-12865-4
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (4 Å)
Structure validation

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数据于2025-07-23公开中

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