Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex
Chao Li, Xue‐Nan Sun, Jan‐Bernd Funcke, Lauri Vanharanta, Xavier Prasanna, Kaitlynn Gov, Yan Li, Megan Virostek, Chanmin Joung, Nolwenn Joffin, Kristiina Kanerva, Ábel Szkalisity, Waldemar Kulig, Leon G. 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, Dayoung Oh, Zhao V. Wang, Ruth Gordillo, Joel Goodman, Richard Wynn, W. Mike Henne, Ilpo Vattulainen, Yan Han, Elina Ikonen, Philipp E. Scherer
Abstract
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.