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

TLDR: Cryo-electron microscopic structures of S-OPA1–coated liposomes in nucleotide-free and GTPγS-bound states reveal that hydrophobic residues in its extended membrane-binding domain are critical for its tubulation activity and indicate that S-opa1 adopts a dynamin-like power stroke membrane remodeling mechanism during mitochondrial inner membrane fusion.

Abstract: 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.