Membrane topology inversion of GGCX mediates cytoplasmic carboxylation for antiviral defense

Okazaki, Tomohiko; Nozaki, Keiji; Morimoto, Nao; Otobe, Yuta; Saito, Riho; Abe, Shuntaro; Okajima, Miyuki; Yoshitane, Hikari; Hatta, Tomohisa; Iemura, Shun-ichiro; Natsume, Tohru; Kosako, Hidetaka; Yamasaki, Miwako; Inoue, Satoshi; Kondo, Takashi; Koseki, Haruhiko; Gotoh, Yukiko

Membrane topology inversion of GGCX mediates cytoplasmic carboxylation for antiviral defense

Okazaki, Tomohiko; Nozaki, Keiji; Morimoto, Nao et al.

Science, 2025, 389(6755), 84-91

Permalink : https://hdl.handle.net/2115/95934

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/95934
タイトル	Membrane topology inversion of GGCX mediates cytoplasmic carboxylation for antiviral defense
著者	Okazaki, Tomohiko ; Nozaki, Keiji ; Morimoto, Nao ; Otobe, Yuta ; Saito, Riho ; Abe, Shuntaro ; Okajima, Miyuki ; Yoshitane, Hikari ; Hatta, Tomohisa ; Iemura, Shun-ichiro ; Natsume, Tohru ; Kosako, Hidetaka ; Yamasaki, Miwako ; Inoue, Satoshi ; Kondo, Takashi ; Koseki, Haruhiko ; Gotoh, Yukiko
e-Rad_Researcher 50724598 著者名 Okazaki, Tomohiko
著者名 Nozaki, Keiji
e-Rad_Researcher 30762249 著者名 Morimoto, Nao
著者名 Otobe, Yuta
著者名 Saito, Riho
著者名 Abe, Shuntaro
著者名 Okajima, Miyuki
著者名 Yoshitane, Hikari
著者名 Hatta, Tomohisa
著者名 Iemura, Shun-ichiro
著者名 Natsume, Tohru
著者名 Kosako, Hidetaka
e-Rad_Researcher 10431305 著者名 Yamasaki, Miwako
著者名 Inoue, Satoshi
著者名 Kondo, Takashi
著者名 Koseki, Haruhiko
著者名 Gotoh, Yukiko
言語	英語
発行日	2025-07-03
出版者	The American Association for the Advancement of Science（AAAS）
収録物名	Science
巻(号)	389(6755)
ページ	84-91
抄録	Mitochondrial antiviral signaling protein (MAVS) is an adaptor involved in antiviral immunity, but its regulation is not fully understood. We identified carboxylation of MAVS by vitamin K (VK)-dependent gamma-glutamyl carboxylase (GGCX), which was unexpected owing to the reported membrane topology of GGCX. We found that GGCX could undergo topology inversion to carboxylate MAVS within the cytoplasm. This carboxylation enhanced the ability of MAVS to induce type I interferons while suppressing the induction of apoptosis. Genetic knockout of GGCX, a VK-free diet, or depletion of VK by inhibiting VK epoxide reductase 1 with warfarin increased viral susceptibility in mice. Thus, we identified a MAVS regulatory mechanism-the existence of cytoplasmic protein carboxylation and topological inversion of GGCX-and demonstrated how modulating VK levels may influence antiviral defense.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on July 3, 2025; DOI: 10.1126/science.adk9967
PISSN	0036-8075
関連情報	PMID 40608933
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1126/science.adk9967