Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding

eLife

Tongxin Niu¹  Xiaoyun Pang²  Yan Zhang²  Yujia Zhai²  Wenbo Chen³  Danyang Zhang³  Jun Ma³  Chunmei Zhu³  Fei Sun⁴ 

[1] Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;University of Chinese Academy of Sciences, Beijing, China;National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;University of Chinese Academy of Sciences, Beijing, China;Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;

关键词: cryo-electron microscopy;    conformational change;    mitochondrial fusion;    membrane tubulation;    OPA1;    Human;   

DOI  :  10.7554/eLife.50294

来源: publisher

【 摘 要 】

Mammalian mitochondrial inner membrane fusion is mediated by optic atrophy 1 (OPA1). Under physiological conditions, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (L-OPA1) and a soluble short isoform (S-OPA1). A combination of L-OPA1 and S-OPA1 is essential for efficient membrane fusion; however, the relevant mechanism is not well understood. In this study, we investigate the cryo-electron microscopic structures of S-OPA1–coated liposomes in nucleotide-free and GTPγS-bound states. S-OPA1 exhibits a general dynamin-like structure and can assemble onto membranes in a helical array with a dimer building block. We reveal that hydrophobic residues in its extended membrane-binding domain are critical for its tubulation activity. The binding of GTPγS triggers a conformational change and results in a rearrangement of the helical lattice and tube expansion similar to that of S-Mgm1. These observations indicate that S-OPA1 adopts a dynamin-like power stroke membrane remodeling mechanism during mitochondrial inner membrane fusion.

【 授权许可】

CC BY