Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex

• 成果类型: Article
• 署名作者: Li, Chao; Sun, Xue-Nan; Funcke, Jan-Bernd; Vanharanta, Lauri; Prasanna, Xavier; Gov, Kaitlynn; Li, Yan; Virostek, Megan; Joung, Chanmin; Joffin, Nolwenn; Kanerva, Kristiina; Szkalisity, Abel; Kulig, Waldemar; Straub, Leon; Chen, Shiuhwei; Velasco, Joselin; Cobb, Ayanna; La Padula, Davide; Wang, May-Yun; Onodera, Toshiharu; Voros, Csaba; Kim, Dae-Seok; Kim, Min; Varlamov, Oleg; Li, Yang; Liu, Chen; Nawrocki, Andrea R.; Zhao, Shangang; Oh, Da Young; Wang, Zhao V.; Gordillo, Ruth; Goodman, Joel M.; Wynn, R. Max; Henne, W. Mike; Vattulainen, Ilpo; Han, Yan; Ikonen, Elina; Scherer, Philipp E.
• 署名单位: University of Texas System; University of Texas Southwestern Medical Center; University of Helsinki; University of Helsinki; University of Helsinki; University of Texas System; University of Texas Southwestern Medical Center; Magna Graecia University of Catanzaro; University of Osaka; University of Osaka; HUN-REN; HUN-REN Biological Research Center; Ulsan National Institute of Science & Technology (UNIST); Oregon Health & Science University; Oregon National Primate Research Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Johnson & Johnson; Janssen Pharmaceuticals; University of Texas System; University of Texas at San Antonio; City of Hope; Beckman Research Institute of City of Hope; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adr9755
• 发表日期: 2025-11-06
• 页码: eadr9755
• 关键词: CONGENITAL LIPODYSTROPHY 2/SEIPIN; protein; biogenesis; molprobity; expression; DYNAMICS

摘要

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 similar to 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.