8b8g

Cryo-EM structure of Ca2+-free mTMEM16F F518H mutant in Digitonin

spinqualitylabelsall models 8b8g, resolution 3.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8b8g is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.39Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ANO6_MOUSE Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets, osteoblasts and fetal thymocytes. Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes. Publication Abstract from PubMed TMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca(2+). However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target. Structural basis for the activation of the lipid scramblase TMEM16F.,Arndt M, Alvadia C, Straub MS, Clerico Mosina V, Paulino C, Dutzler R Nat Commun. 2022 Nov 5;13(1):6692. doi: 10.1038/s41467-022-34497-x. PMID:36335104 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA