8tps

nhTMEM16 A444P mutant in lipid nanodiscs with MSP1E3 scaffold protein in the presence of Ca2+ (bent TM6)

spinqualitylabelsall models 8tps, resolution 2.97Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tps is a 2 chain structure with sequence from Fusarium vanettenii 77-13-4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.97Å Ligands: CA, PGW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C7Z7K1_FUSV7 Publication Abstract from PubMed Activation of Ca(2+)-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca(2+) dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at the closed groove of Ca(2+)-bound fungal nhTMEM16 in nanodiscs using cryo-EM. Functional experiments pinpoint lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two pi-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryo-EM structure determination. Structural basis of closed groove scrambling by a TMEM16 protein.,Feng Z, Alvarenga OE, Accardi A Nat Struct Mol Biol. 2024 Apr 29. doi: 10.1038/s41594-024-01284-9. PMID:38684930 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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