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bioRxiv · 10.1101/2021.05.06.442885

An intramolecular scrambling path controlled by a gatekeeper in Xkr8 phospholipid scramblase

Sakuragi, T.·Kanai, R.·Tsutsumi, A.·Narita, H.·Onishi, E.·Miyazaki, T.·Baba, T.·Nakagawa, A.·Kikkawa, M.·Toyoshima, C.·Nagata, S.
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Abstract

Xkr8-Basigin is a phospholipid scramblase at plasma membranes that is activated by kinase or caspase. We investigated its structure at a resolution of 3.8[A]. 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.

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Sakuragi, T., Kanai, R., Tsutsumi, A., Narita, H., Onishi, E., Miyazaki, T., Baba, T., Nakagawa, A., Kikkawa, M., Toyoshima, C., Nagata, S.. 2021-05-06. An intramolecular scrambling path controlled by a gatekeeper in Xkr8 phospholipid scramblase. https://doi.org/10.1101/2021.05.06.442885

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