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eLife Volume 9 ,2020-03-30
Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding
Structural Biology and Molecular Biophysics
Danyang Zhang 1 , 2 Yan Zhang 1 Jun Ma 1 , 2 Chunmei Zhu 1 , 2 Tongxin Niu 3 Wenbo Chen 1 , 2 Xiaoyun Pang 1 Yujia Zhai 1 Fei Sun 1 , 2 , 3
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DOI:10.7554/eLife.50294
Received 2019-07-17, accepted for publication 2020-03-30, Published 2020-03-30
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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.

关键词

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

授权许可

© 2020, Zhang et al
http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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Danyang Zhang,Yan Zhang,Jun Ma,Chunmei Zhu,Tongxin Niu,Wenbo Chen,Xiaoyun Pang,Yujia Zhai,Fei Sun. Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding. eLife ,Vol.9(2020)

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