6QM5

Cryo-EM structure of calcium-bound nhTMEM16 lipid scramblase in DDM

Summary for 6QM5

• Entry DOI: 10.2210/pdb6qm5/pdb
• EMDB information: 4588
• Descriptor: Predicted protein, CALCIUM ION (2 entities in total)
• Functional Keywords: membrane protein, lipid scrambles, tmem16
• Biological source: Nectria haematococca
• Total number of polymer chains: 2
• Total formula weight: 166560.33

Authors

Kalienkova, V.,Clerico Mosina, V.,Bryner, L.,Oostergetel, G.T.,Dutzler, R.,Paulino, C. (deposition date: 2019-02-01, release date: 2019-03-06, Last modification date: 2024-05-15)

Primary citation

Kalienkova, V.,Clerico Mosina, V.,Bryner, L.,Oostergetel, G.T.,Dutzler, R.,Paulino, C.
Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM.
Elife, 8:-, 2019

PubMed Abstract: 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-dependent lipid scramblase, its regulation mechanism has remained elusive. Here, we have used cryo-electron microscopy and functional assays to address this question. Ca-bound and Ca-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 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-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.

PubMed: 30785398
DOI: 10.7554/eLife.44364

Experimental method

ELECTRON MICROSCOPY (3.6 Å)