PT  - JOURNAL ARTICLE
AU  - Takaharu Sakuragi
AU  - Ryuta Kanai
AU  - Akihisa Tsutsumi
AU  - Hirotaka Narita
AU  - Eriko Onishi
AU  - Takuya Miyazaki
AU  - Takeshi Baba
AU  - Atsushi Nakagawa
AU  - Masahide Kikkawa
AU  - Chikashi Toyoshima
AU  - Shigekazu Nagata
TI  - An intramolecular scrambling path controlled by a gatekeeper in Xkr8 phospholipid scramblase
AID  - 10.1101/2021.05.06.442885
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.06.442885
4099  - http://biorxiv.org/content/early/2021/05/06/2021.05.06.442885.short
4100  - http://biorxiv.org/content/early/2021/05/06/2021.05.06.442885.full
AB  - Xkr8-Basigin is a phospholipid scramblase at plasma membranes that is activated by kinase or caspase. We investigated its structure at a resolution of 3.8Å. Its membrane-spanning region had a cuboid-like structure stabilized by salt bridges between hydrophilic residues in helices in the lipid layer. The molecule carried phosphatidylcholine in a cleft on the surface that may function as an entry site for phospholipids. Five charged residues placed from top to bottom inside the molecule were essential for providing a path for scrambling phospholipids. A tryptophan residue was present at the extracellular end of the pathway and its mutation made the Xkr8-Basigin complex constitutively active, indicating its function as a gatekeeper. The structure of Xkr8-Basigin provides novel insights into the molecular mechanisms underlying phospholipid scrambling.Competing Interest StatementThe authors have declared no competing interest.