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TitleThe tertiary structure of the human Xkr8-Basigin complex that scrambles phospholipids at plasma membranes.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 10, Page 825-834, Year 2021
Publish dateOct 8, 2021
AuthorsTakaharu Sakuragi / Ryuta Kanai / Akihisa Tsutsumi / Hirotaka Narita / Eriko Onishi / Kohei Nishino / Takuya Miyazaki / Takeshi Baba / Hidetaka Kosako / Atsushi Nakagawa / Masahide Kikkawa / Chikashi Toyoshima / Shigekazu Nagata /
PubMed AbstractXkr8-Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. We combined cryo-EM and X-ray crystallography to investigate its structure at an overall resolution of 3. ...Xkr8-Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. We combined cryo-EM and X-ray crystallography to investigate its structure at an overall resolution of 3.8 Å. Its membrane-spanning region carrying 22 charged amino acids adopts a cuboid-like structure stabilized by salt bridges between hydrophilic residues in transmembrane helices. Phosphatidylcholine binding was observed in a hydrophobic cleft on the surface exposed to the outer leaflet of the plasma membrane. Six charged residues placed from top to bottom inside the molecule were essential for scrambling phospholipids in inward and outward directions, apparently providing a pathway for their translocation. A tryptophan residue was present between the head group of phosphatidylcholine and the extracellular end of the path. Its mutation to alanine made the Xkr8-Basigin complex constitutively active, indicating that it plays a vital role in regulating its scramblase activity. The structure of Xkr8-Basigin provides insights into the molecular mechanisms underlying phospholipid scrambling.
External linksNat Struct Mol Biol / PubMed:34625749 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.123 - 3.8 Å
Structure data

EMDB-30636, PDB-7dce:
Cryo-EM structure of human XKR8-basigin complex bound to Fab fragment
Method: EM (single particle) / Resolution: 3.8 Å

PDB-7d9z:
Crystal structure of anti-basigin Fab fragment
Method: X-RAY DIFFRACTION / Resolution: 1.123 Å

PDB-7daa:
Crystal structure of basigin complexed with anti-basigin Fab fragment
Method: X-RAY DIFFRACTION / Resolution: 2.51 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-FLC:
CITRATE ANION / Citric acid

ChemComp-HOH:
WATER / Water

ChemComp-CD:
Unknown entry

ChemComp-DLP:
1,2-DILINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM / Phosphatidylcholine

Source
  • homo sapiens (human)
  • oryctolagus cuniculus (rabbit)
KeywordsIMMUNE SYSTEM / Fab / antibody / basigin / CHAPERONE / complex / TRANSPORT PROTEIN / XKR8 / scramblase / phospholipid

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