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The role of the C-terminal tail region as a plug to regulate XKR8 lipid scramblase.
Sakuragi, Takaharu; Kanai, Ryuta; Otani, Mayumi; Kikkawa, Masahide; Toyoshima, Chikashi; Nagata, Shigekazu.
Afiliación
  • Sakuragi T; Laboratory of Biochemistry and Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
  • Kanai R; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
  • Otani M; Laboratory of Biochemistry and Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
  • Kikkawa M; Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Toyoshima C; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
  • Nagata S; Laboratory of Biochemistry and Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan. Electronic address: snagata@ifrec.osaka-u.ac.jp.
J Biol Chem ; 300(3): 105755, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38364890
ABSTRACT
XK-related 8 (XKR8), in complex with the transmembrane glycoprotein basigin, functions as a phospholipid scramblase activated by the caspase-mediated cleavage or phosphorylation of its C-terminal tail. It carries a putative phospholipid translocation path of multiple hydrophobic and charged residues in the transmembrane region. It also has a crucial tryptophan at the exoplasmic end of the path that regulates its scrambling activity. We herein investigated the tertiary structure of the human XKR8-basigin complex embedded in lipid nanodiscs at an overall resolution of 3.66 Å. We found that the C-terminal tail engaged in intricate polar and van der Waals interactions with a groove at the cytoplasmic surface of XKR8. These interactions maintained the inactive state of XKR8. Point mutations to disrupt these interactions strongly enhanced the scrambling activity of XKR8, suggesting that the activation of XKR8 is mediated by releasing the C-terminal tail from the cytoplasmic groove. We speculate that the cytoplasmic tail region of XKR8 functions as a plug to prevent the scrambling of phospholipids.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transferencia de Fosfolípidos / Proteínas Reguladoras de la Apoptosis / Basigina / Proteínas de la Membrana Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Transferencia de Fosfolípidos / Proteínas Reguladoras de la Apoptosis / Basigina / Proteínas de la Membrana Límite: Humans Idioma: En Revista: J Biol Chem Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos