National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
RC2-DK118620
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01- DK55758
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01-DK099110
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01-DK127274
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
R01-DK131537
米国
引用
ジャーナル: Science / 年: 2025 タイトル: Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex. 著者: Chao Li / Xue-Nan Sun / Jan-Bernd Funcke / Lauri Vanharanta / Xavier Prasanna / Kaitlynn Gov / Yan Li / Megan Virostek / Chanmin Joung / Nolwenn Joffin / Kristiina Kanerva / Abel Szkalisity / ...著者: Chao Li / Xue-Nan Sun / Jan-Bernd Funcke / Lauri Vanharanta / Xavier Prasanna / Kaitlynn Gov / Yan Li / Megan Virostek / Chanmin Joung / Nolwenn Joffin / Kristiina Kanerva / Abel Szkalisity / Waldemar Kulig / Leon Straub / Shiuhwei Chen / Joselin Velasco / Ayanna Cobb / Davide La Padula / May-Yun Wang / Toshiharu Onodera / Csaba Vörös / Dae-Seok Kim / Min Kim / Oleg Varlamov / Yang Li / Chen Liu / Andrea R Nawrocki / Shangang Zhao / Da Young Oh / Zhao V Wang / Ruth Gordillo / Joel M Goodman / R Max Wynn / W Mike Henne / Ilpo Vattulainen / Yan Han / Elina Ikonen / Philipp E Scherer / 要旨: The microprotein adipogenin (Adig) is predominantly expressed in adipose tissues. Here, we found that Adig interacts with seipin to form a stable, rigid complex. We present the structure of the ...The microprotein adipogenin (Adig) is predominantly expressed in adipose tissues. Here, we found that Adig interacts with seipin to form a stable, rigid complex. We present the structure of the seipin-Adig complex at an overall resolution of ~3.0 angstroms. The structure revealed that mammalian seipin assembles into two distinct oligomeric forms: undecamers and dodecamers. Adig selectively bound to the dodecameric form and enhanced seipin assembly by bridging and stabilizing adjacent subunits. Functionally, this complex promoted lipid droplet development at both early and late stages. In transgenic mice, adipocyte-specific overexpression of Adig increased fat mass and enlarged lipid droplets, whereas Adig deletion disrupted triglyceride accumulation in brown adipose tissues. Thus, Adig can modulate lipid storage through its structural and functional interactions with seipin.
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