8CT9
CryoEM structure of human S-OPA1 assembled on lipid membrane in membrane-distal state
This is a non-PDB format compatible entry.
Summary for 8CT9
| Entry DOI | 10.2210/pdb8ct9/pdb |
| EMDB information | 26984 |
| Descriptor | Dynamin-like 120 kDa protein, mitochondrial, CARDIOLIPIN (2 entities in total) |
| Functional Keywords | gtpase, polymer, filament, membrane, remodeling, fusion, mitochondria, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 34 |
| Total formula weight | 3934590.74 |
| Authors | Du Pont, K.E.,Aydin, H. (deposition date: 2022-05-13, release date: 2023-08-30, Last modification date: 2024-11-13) |
| Primary citation | von der Malsburg, A.,Sapp, G.M.,Zuccaro, K.E.,von Appen, A.,Moss 3rd, F.R.,Kalia, R.,Bennett, J.A.,Abriata, L.A.,Dal Peraro, M.,van der Laan, M.,Frost, A.,Aydin, H. Structural mechanism of mitochondrial membrane remodelling by human OPA1. Nature, 620:1101-1108, 2023 Cited by PubMed Abstract: Distinct morphologies of the mitochondrial network support divergent metabolic and regulatory processes that determine cell function and fate. The mechanochemical GTPase optic atrophy 1 (OPA1) influences the architecture of cristae and catalyses the fusion of the mitochondrial inner membrane. Despite its fundamental importance, the molecular mechanisms by which OPA1 modulates mitochondrial morphology are unclear. Here, using a combination of cellular and structural analyses, we illuminate the molecular mechanisms that are key to OPA1-dependent membrane remodelling and fusion. Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain. A conserved loop within the paddle domain inserts deeply into the bilayer, further stabilizing the interactions with cardiolipin-enriched membranes. OPA1 dimerization through the paddle domain promotes the helical assembly of a flexible OPA1 lattice on the membrane, which drives mitochondrial fusion in cells. Moreover, the membrane-bending OPA1 oligomer undergoes conformational changes that pull the membrane-inserting loop out of the outer leaflet and contribute to the mechanics of membrane remodelling. Our findings provide a structural framework for understanding how human OPA1 shapes mitochondrial morphology and show us how human disease mutations compromise OPA1 functions. PubMed: 37612504DOI: 10.1038/s41586-023-06441-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (6.8 Å) |
Structure validation
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