6e1o

afTMEM16 reconstituted in nanodiscs in the presence of Ca2+ and ceramide 24:0

Loading... Status: waiting for Mol* initialization Structural highlights 6e1o is a 2 chain structure with sequence from Aspfu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 8K6, CA, D10, D12, HEX Related: 6dz7, 6e0h Gene: AFUA_4G02970 (ASPFU) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The lipid distribution of plasma membranes of eukaryotic cells is asymmetric and phospholipid scramblases disrupt this asymmetry by mediating the rapid, nonselective transport of lipids down their concentration gradients. As a result, phosphatidylserine is exposed to the outer leaflet of membrane, an important step in extracellular signaling networks controlling processes such as apoptosis, blood coagulation, membrane fusion and repair. Several TMEM16 family members have been identified as Ca(2+)-activated scramblases, but the mechanisms underlying their Ca(2+)-dependent gating and their effects on the surrounding lipid bilayer remain poorly understood. Here, we describe three high-resolution cryo-electron microscopy structures of a fungal scramblase from Aspergillus fumigatus, afTMEM16, reconstituted in lipid nanodiscs. These structures reveal that Ca(2+)-dependent activation of the scramblase entails global rearrangement of the transmembrane and cytosolic domains. These structures, together with functional experiments, suggest that activation of the protein thins the membrane near the transport pathway to facilitate rapid transbilayer lipid movement. Structural basis of Ca(2+)-dependent activation and lipid transport by a TMEM16 scramblase.,Falzone ME, Rheinberger J, Lee BC, Peyear T, Sasset L, Raczkowski AM, Eng ET, Di Lorenzo A, Andersen OS, Nimigean CM, Accardi A Elife. 2019 Jan 16;8. pii: 43229. doi: 10.7554/eLife.43229. PMID:30648972 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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