该课题组研究人员发现Adig与seipin相互作用形成稳定的刚性复合物。小组以~3.0埃的总分辨率给出了sepin-Adig配合物的结构。该结构揭示了哺乳动物的seipin组装成两种不同的低聚形式：十一聚体和十二聚体。Adig选择性地结合到十二聚体上，并通过桥接和稳定相邻亚基来增强sepin组装。在功能上，这个复合物在早期和晚期都促进了脂滴的发育。在转基因小鼠中，脂肪细胞特异性Adig的过表达增加了脂肪量和脂滴的增大，而Adig的缺失破坏了棕色脂肪组织中甘油三酯的积累。因此，Adig可以通过其与seipin的结构和功能相互作用来调节脂质储存。
据悉，微蛋白脂肪原（Adig）主要在脂肪组织中表达。
附：英文原文
Title: Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex
Author: 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 Vrs, 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
Issue&Volume: 2025-11-06
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.
DOI: adr9755
Source: https://www.science.org/doi/10.1126/science.adr9755