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TitleCryo-EM structures of the caspase-activated protein XKR9 involved in apoptotic lipid scrambling.
Journal, issue, pagesElife, Vol. 10, Year 2021
Publish dateJul 15, 2021
AuthorsMonique S Straub / Carolina Alvadia / Marta Sawicka / Raimund Dutzler /
PubMed AbstractThe exposure of the negatively charged lipid phosphatidylserine on the cell surface, catalyzed by lipid scramblases, is an important signal for the clearance of apoptotic cells by macrophages. The ...The exposure of the negatively charged lipid phosphatidylserine on the cell surface, catalyzed by lipid scramblases, is an important signal for the clearance of apoptotic cells by macrophages. The protein XKR9 is a member of a conserved family that has been associated with apoptotic lipid scrambling. Here, we describe structures of full-length and caspase-treated XKR9 from in complex with a synthetic nanobody determined by cryo-electron microscopy. The 43 kDa monomeric membrane protein can be divided into two structurally related repeats, each containing four membrane-spanning segments and a helix that is partly inserted into the lipid bilayer. In the full-length protein, the C-terminus interacts with a hydrophobic pocket located at the intracellular side acting as an inhibitor of protein function. Cleavage by caspase-3 at a specific site releases 16 residues of the C-terminus, thus making the pocket accessible to the cytoplasm. Collectively, the work has revealed the unknown architecture of the XKR family and has provided initial insight into its activation by caspases.
External linksElife / PubMed:34263724 / PubMed Central
MethodsEM (single particle)
Resolution3.66 - 4.3 Å
Structure data

13155

7p14

EMDB-13155: Cryo-EM density of full-length rXKR9 in complex with a sybody at 3.66A
PDB-7p14: Structure of full-length rXKR9 in complex with a sybody at 3.66A
Method: EM (single particle) / Resolution: 3.66 Å

13157

7p16

EMDB-13157: Cryo-EM density of caspase-3 cleaved rXKR9 in complex with a sybody at 4.3A
PDB-7p16: Structure of caspase-3 cleaved rXKR9 in complex with a sybody at 4.3A
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-PLC:
DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipid*YM

ChemComp-P5S:
O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine

Source
  • rattus norvegicus (Norway rat)
  • synthetic construct (others)
KeywordsMEMBRANE PROTEIN / small membrane protein / in complex with sybody / apoptotic lipid scrambling

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