6psy

From Proteopedia

Cryo-EM structure of S. cerevisiae Drs2p-Cdc50p in the autoinhibited apo form

6psy, resolution 2.80Å

Structural highlights

6psy is a 2 chain structure with sequence from Saccharomyces cerevisiae W303. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.8Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ATC3_YEAST This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of phospholipids (Potential). Seems to be involved in ribosome assembly.

Publication Abstract from PubMed

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 A and 3.3 A 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 degrees 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.

Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p.,Bai L, Kovach A, You Q, Hsu HC, Zhao G, Li H Nat Commun. 2019 Sep 12;10(1):4142. doi: 10.1038/s41467-019-12191-9. PMID:31515475^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bai L, Kovach A, You Q, Hsu HC, Zhao G, Li H. Autoinhibition and activation mechanisms of the eukaryotic lipid flippase Drs2p-Cdc50p. Nat Commun. 2019 Sep 12;10(1):4142. doi: 10.1038/s41467-019-12191-9. PMID:31515475 doi:http://dx.doi.org/10.1038/s41467-019-12191-9