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TitleCryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateMar 31, 2020
AuthorsDanyang Zhang / Yan Zhang / Jun Ma / Chunmei Zhu / Tongxin Niu / Wenbo Chen / Xiaoyun Pang / Yujia Zhai / Fei Sun /
PubMed AbstractMammalian 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- ...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.
External linksElife / PubMed:32228866 / PubMed Central
MethodsEM (subtomogram averaging) / EM (helical sym.)
Resolution15.0 - 31.7 Å
Structure data

EMDB-0722:
Full length S-OPA1 coated liposome tube at nucleotide-free state
Method: EM (subtomogram averaging) / Resolution: 31.7 Å

EMDB-9901:
Helical Reconstruction of S-OPA1 At Nucleotide-free State
Method: EM (helical sym.) / Resolution: 15.0 Å

EMDB-9902:
S-OPA1 coated liposome tube at GTPgamaS bound state
Method: EM (subtomogram averaging) / Resolution: 23.2 Å

EMDB-9903:
S-OPA1 coated liposome tube at nucleotide-free state
Method: EM (subtomogram averaging) / Resolution: 23.0 Å

Source
  • Homo sapiens (human)

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