ID | 116966 |
Author |
Sakuragi, Takaharu
Osaka University
Kanai, Ryuta
The University of Tokyo
Tsutsumi, Akihisa
The University of Tokyo
Narita, Hirotaka
Osaka University|Japan Aerospace Exploration Agency
Onishi, Eriko
Osaka University
Nishino, Kohei
Tokushima University
Miyazaki, Takuya
Chugai Pharmaceutical
Baba, Takeshi
Chugai Pharmaceutical
Kosako, Hidetaka
Tokushima University
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Nakagawa, Atsushi
Osaka University
Kikkawa, Masahide
The University of Tokyo
Toyoshima, Chikashi
The University of Tokyo
Nagata, Shigekazu
Osaka University
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Content Type |
Journal Article
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Description | 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.
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Journal Title |
Nature Structural & Molecular Biology
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ISSN | 15459993
15459985
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NCID | AA11879900
AA11952261
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Publisher | Springer Nature
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Volume | 28
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Issue | 10
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Start Page | 825
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End Page | 834
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Published Date | 2021-10-08
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Rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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language |
eng
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Publisher
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departments |
Institute of Advanced Medical Sciences
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