6PSX

Cryo-EM structure of S. cerevisiae Drs2p-Cdc50p in the PI4P-activated form

Summary for 6PSX

• Entry DOI: 10.2210/pdb6psx/pdb
• EMDB information: 20467 20468
• Descriptor: Probable phospholipid-transporting ATPase DRS2, Cell division control protein 50, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, phospholipid flippase, p-type atpase, translocase
• Biological source: Saccharomyces cerevisiae W303 (yeast); More
• Total number of polymer chains: 2
• Total formula weight: 199830.91

Authors

Bai, L.,Li, H. (deposition date: 2019-07-14, release date: 2019-09-25, Last modification date: 2024-10-09)

Primary citation

Bai, L.,Kovach, A.,You, Q.,Hsu, H.C.,Zhao, G.,Li, H.
Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p.
Nat Commun, 10:4142-4142, 2019

PubMed Abstract: The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry. The enzyme complex exists in an autoinhibited form in the absence of an activator and is specifically activated by phosphatidylinositol-4-phosphate (PI4P), although the underlying mechanisms have been unclear. Here we report the cryo-EM structures of intact Drs2p-Cdc50p isolated from S. cerevisiae in apo form and in the PI4P-activated form at 2.8 Å and 3.3 Å resolution, respectively. The structures reveal that the Drs2p C-terminus lines a long groove in the cytosolic regulatory region to inhibit the flippase activity. PIP4 binding in a cytosol-proximal membrane region triggers a 90° rotation of a cytosolic helix switch that is located just upstream of the inhibitory C-terminal peptide. The rotation of the helix switch dislodges the C-terminus from the regulatory region, activating the flippase.

PubMed: 31515475
DOI: 10.1038/s41467-019-12191-9

Experimental method

ELECTRON MICROSCOPY (3.3 Å)