6qmb

Cryo-EM structure of calcium-bound nhTMEM16 lipid scramblase in nanodisc (closed state)

Loading... Status: waiting for Mol* initialization Structural highlights 6qmb 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 Scramblases catalyze the movement of lipids between both leaflets of a bilayer. Whereas the X-ray structure of the protein nhTMEM16 has previously revealed the architecture of a Ca(2+)-dependent lipid scramblase, its regulation mechanism has remained elusive. Here, we have used cryo-electron microscopy and functional assays to address this question. Ca(2+)-bound and Ca(2+)-free conformations of nhTMEM16 in detergent and lipid nanodiscs illustrate the interactions with its environment and they reveal the conformational changes underlying its activation. In this process, Ca(2+)-binding induces a stepwise transition of the catalytic subunit cavity, converting a closed cavity that is shielded from the membrane in the absence of ligand, into a polar furrow that becomes accessible to lipid headgroups in the Ca(2+)-bound state. Additionally, our structures demonstrate how nhTMEM16 distorts the membrane at both entrances of the subunit cavity, thereby decreasing the energy barrier for lipid movement. Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM.,Kalienkova V, Clerico Mosina V, Bryner L, Oostergetel GT, Dutzler R, Paulino C Elife. 2019 Feb 20;8. pii: 44364. doi: 10.7554/eLife.44364. PMID:30785398 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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