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bioRxiv · 10.1101/528042

Cryo-EM structures reveal a conformational change of SOPA1 during mitochondrial inner membrane fusion

Zhang, D.·Zhang, Y.·Ma, J.·Niu, T.·Chen, W.·Pang, X.·Zhai, Y.·Sun, F.
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Abstract

Mammalian mitochondrial inner membrane fusion is mediated by OPA1(optic atrophy 1). Under physiological condition, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (LOPA1) and a soluble short isoform (SOPA1). A combination of LOPA1 and SOPA1 are required for membrane fusion, however, the relevant mechanism is not well understood. In this study, we investigate the cryo-EM structures of SOPA1 coated liposome tube at nucleotide-free and GTP{gamma}S bound states. SOPA1 exhibits a general structure of dynamin family and can assemble onto membrane in a helical array with a building block of dimer and thus induce membrane tubulation. A predicted amphipathic helix is discovered to mediate the tubulation activity of SOPA1. The binding of GTP{gamma}S causes a conformational rotation between GTPase domain and stalk region, and then induces a rearrangement of the helical array and an expansion of the tube, which is opposite to the behavior of other dynamin proteins, suggesting a unique role of SOPA1 in the fusion of mitochondrial inner membrane.

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Zhang, D., Zhang, Y., Ma, J., Niu, T., Chen, W., Pang, X., Zhai, Y., Sun, F.. 2019-01-23. Cryo-EM structures reveal a conformational change of SOPA1 during mitochondrial inner membrane fusion. https://doi.org/10.1101/528042

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