6oy3 | pdb_00006oy3

nhTMEM16 L302A +Ca2+ in nanodiscs

Loading... Status: waiting for Mol* initialization Structural highlights 6oy3 is a 2 chain structure with sequence from Fusarium solani subsp. pisi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Gene: NECHADRAFT_66456 (Fusarium solani subsp. pisi) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Both lipid and ion translocation by Ca(2+)-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(2+)-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. Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca(2+)-bound nhTMEM16.,Khelashvili G, Falzone ME, Cheng X, Lee BC, Accardi A, Weinstein H Nat Commun. 2019 Oct 31;10(1):4972. doi: 10.1038/s41467-019-12865-4. PMID:31672969 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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