6qpi
Cryo-EM structure of calcium-free mTMEM16F lipid scramblase in nanodisc
Structural highlights
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.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel. The cryo-EM data of mTMEM16F in absence and presence of Ca(2+) define the ligand-free closed conformation of the protein and the structure of a Ca(2+)-bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, both functions appear to be mediated by alternate protein conformations that are at equilibrium in the ligand-bound state. Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F.,Alvadia C, Lim NK, Clerico Mosina V, Oostergetel GT, Dutzler R, Paulino C Elife. 2019 Feb 20;8. pii: 44365. doi: 10.7554/eLife.44365. PMID:30785399[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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