Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	OPA1 helical structures give perspective to mitochondrial dysfunction.
Journal, issue, pages	Nature, Vol. 620, Issue 7976, Page 1109-1116, Year 2023
Publish date	Aug 23, 2023
Authors	Sarah B Nyenhuis / Xufeng Wu / Marie-Paule Strub / Yang-In Yim / Abigail E Stanton / Valentina Baena / Zulfeqhar A Syed / Bertram Canagarajah / John A Hammer / Jenny E Hinshaw /
PubMed Abstract	Dominant optic atrophy is one of the leading causes of childhood blindness. Around 60-80% of cases are caused by mutations of the gene that encodes optic atrophy protein 1 (OPA1), a protein that has ...Dominant optic atrophy is one of the leading causes of childhood blindness. Around 60-80% of cases are caused by mutations of the gene that encodes optic atrophy protein 1 (OPA1), a protein that has a key role in inner mitochondrial membrane fusion and remodelling of cristae and is crucial for the dynamic organization and regulation of mitochondria. Mutations in OPA1 result in the dysregulation of the GTPase-mediated fusion process of the mitochondrial inner and outer membranes. Here we used cryo-electron microscopy methods to solve helical structures of OPA1 assembled on lipid membrane tubes, in the presence and absence of nucleotide. These helical assemblies organize into densely packed protein rungs with minimal inter-rung connectivity, and exhibit nucleotide-dependent dimerization of the GTPase domains-a hallmark of the dynamin superfamily of proteins. OPA1 also contains several unique secondary structures in the paddle domain that strengthen its membrane association, including membrane-inserting helices. The structural features identified in this study shed light on the effects of pathogenic point mutations on protein folding, inter-protein assembly and membrane interactions. Furthermore, mutations that disrupt the assembly interfaces and membrane binding of OPA1 cause mitochondrial fragmentation in cell-based assays, providing evidence of the biological relevance of these interactions.
External links	Nature / PubMed:37612506
Methods	EM (helical sym.)
Resolution	2.88 - 9.68 Å
Structure data	28063 8eew 8eff 8efr EMDB-28063, PDB-8eew: CryoEM of the soluble OPA1 dimer from the GDP-AlFx bound helical assembly on a lipid membrane PDB-8eff: CryoEM of the soluble OPA1 tetramer from the GDP-AlFx bound helical assembly on a lipid membrane PDB-8efr: CryoEM of the soluble OPA1 interfaces with GDP-AlFx bound from the helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 5.48 Å 28074 8ef7 8efs 8eft EMDB-28074, PDB-8ef7: CryoEM of the soluble OPA1 dimer from the apo helical assembly on a lipid membrane PDB-8efs: CryoEM of the soluble OPA1 tetramer from the apo helical assembly on a lipid membrane PDB-8eft: CryoEM of the soluble OPA1 interfaces from the apo helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 9.68 Å EMDB-40192: CryoEM map of the locally refined soluble OPA1 Z-clip from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 3.86 Å EMDB-40193: CryoEM map of the locally refined soluble OPA1 Z-clip from the apo helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 5.8 Å EMDB-40197: CryoEM map of soluble OPA1 from the GDP-AlFx bound N-terminal helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 6.51 Å EMDB-40198: CryoEM map of the locally refined interface-8 of soluble OPA1 from the GDP-AlFx bound N-terminal helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 2.99 Å EMDB-40200: CryoEM map of the locally refined dimer of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 3.34 Å EMDB-40202: CryoEM map of the locally refined dimer of soluble OPA1 from the apo bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 6.55 Å EMDB-40203: CryoEM map of the locally refined interfaces-1,2,3 of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 2.95 Å EMDB-40204: CryoEM map of the locally refined interfaces-1,2,3 of soluble OPA1 from the apo bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 5.51 Å EMDB-40210: CryoEM map of the locally refined interface-4 of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 2.88 Å EMDB-40211: CryoEM map of the locally refined interface-4 of soluble OPA1 from the apo bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 4.71 Å EMDB-40212: CryoEM map of the locally refined interface-7 of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 3.08 Å EMDB-40213: CryoEM map of the locally refined interface-7 of soluble OPA1 from the apo bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 5.16 Å EMDB-40214: CryoEM map of the locally refined interfaces-5,6 of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 2.98 Å EMDB-40215: CryoEM map of the locally refined monomer-A of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 3.23 Å EMDB-40216: CryoEM map of the locally refined monomer-B of soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 3.15 Å EMDB-40217: CryoEM map of the locally refined cardiolipin containing monolayer and soluble OPA1 paddles from the GDP-AlFx bound helical assembly on a lipid membrane Method: EM (helical sym.) / Resolution: 2.91 Å
Chemicals	ChemComp-GDP: GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying moleculeYM / Guanosine diphosphate ChemComp-ALF: TETRAFLUOROALUMINATE ION ChemComp-MG: Unknown entry ChemComp-K*: Unknown entry
Source	homo sapiens (human)
Keywords	LIPID BINDING PROTEIN / GTPase / Dynamin-family protein / mitochondrial fusion protein / mitochondria / Optic Atrophy