- EMDB-40217: CryoEM map of the locally refined cardiolipin containing monolaye... -
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基本情報
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データベース: EMDB / ID: EMD-40217
タイトル
CryoEM map of the locally refined cardiolipin containing monolayer and soluble OPA1 paddles from the GDP-AlFx bound helical assembly on a lipid membrane
マップデータ
CryoEM map of the locally refined cardiolipin containing monolayer and soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane
試料
複合体: sOPA1 helical assembly on a lipid membrane
タンパク質・ペプチド: sOPA1 protein
キーワード
GTPase / Dynamin-family protein / mitochondrial fusion protein / mitochondria / Optic Atrophy / LIPID BINDING PROTEIN
機能・相同性
機能・相同性情報
Regulation of Apoptosis / membrane tubulation / inner mitochondrial membrane organization / dynamin GTPase / cardiolipin binding / mitochondrial genome maintenance / phosphatidic acid binding / mitochondrial fission / GTP metabolic process / mitochondrial fusion ...Regulation of Apoptosis / membrane tubulation / inner mitochondrial membrane organization / dynamin GTPase / cardiolipin binding / mitochondrial genome maintenance / phosphatidic acid binding / mitochondrial fission / GTP metabolic process / mitochondrial fusion / axonal transport of mitochondrion / negative regulation of release of cytochrome c from mitochondria / mitochondrial crista / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / axon cytoplasm / Mitochondrial protein degradation / visual perception / mitochondrion organization / neural tube closure / mitochondrial membrane / mitochondrial intermembrane space / cellular senescence / protein complex oligomerization / microtubule binding / microtubule / mitochondrial outer membrane / mitochondrial inner membrane / GTPase activity / apoptotic process / dendrite / GTP binding / negative regulation of apoptotic process / magnesium ion binding / mitochondrion / nucleoplasm / membrane / cytoplasm / cytosol 類似検索 - 分子機能
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
米国
引用
ジャーナル: Nature / 年: 2023 タイトル: OPA1 helical structures give perspective to mitochondrial dysfunction. 著者: 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 / 要旨: 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.
CryoEM half map A of the locally refined cardiolipin containing monolayer and soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane
CryoEM half map B of the locally refined cardiolipin containing monolayer and soluble OPA1 from the GDP-AlFx bound helical assembly on a lipid membrane