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- EMDB-32227: Cryo-EM structure of amyloid fibril formed by full-length human SOD1 -
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Open data
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Basic information
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Title | Cryo-EM structure of amyloid fibril formed by full-length human SOD1 | ||||||||||||
![]() | The cryo-EM map of SOD1 fibril. | ||||||||||||
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![]() | Amyloid fibril / PROTEIN FIBRIL | ||||||||||||
Function / homology | ![]() action potential initiation / neurofilament cytoskeleton organization / positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / protein phosphatase 2B binding / regulation of organ growth / relaxation of vascular associated smooth muscle / response to superoxide / retrograde axonal transport / anterograde axonal transport / peripheral nervous system myelin maintenance ...action potential initiation / neurofilament cytoskeleton organization / positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / protein phosphatase 2B binding / regulation of organ growth / relaxation of vascular associated smooth muscle / response to superoxide / retrograde axonal transport / anterograde axonal transport / peripheral nervous system myelin maintenance / regulation of protein kinase activity / regulation of T cell differentiation in thymus / retina homeostasis / superoxide anion generation / negative regulation of cholesterol biosynthetic process / auditory receptor cell stereocilium organization / hydrogen peroxide biosynthetic process / myeloid cell homeostasis / positive regulation of catalytic activity / muscle cell cellular homeostasis / regulation of GTPase activity / heart contraction / superoxide metabolic process / superoxide dismutase / negative regulation of reproductive process / Detoxification of Reactive Oxygen Species / negative regulation of developmental process / transmission of nerve impulse / superoxide dismutase activity / neuronal action potential / regulation of multicellular organism growth / response to axon injury / ectopic germ cell programmed cell death / ovarian follicle development / positive regulation of phagocytosis / axon cytoplasm / glutathione metabolic process / embryo implantation / : / dendrite cytoplasm / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / removal of superoxide radicals / reactive oxygen species metabolic process / positive regulation of superoxide anion generation / thymus development / regulation of mitochondrial membrane potential / positive regulation of cytokine production / locomotory behavior / determination of adult lifespan / sensory perception of sound / response to hydrogen peroxide / placenta development / mitochondrial intermembrane space / small GTPase binding / regulation of blood pressure / negative regulation of inflammatory response / Platelet degranulation / peroxisome / protein-folding chaperone binding / gene expression / response to heat / cytoplasmic vesicle / spermatogenesis / response to ethanol / intracellular iron ion homeostasis / negative regulation of neuron apoptotic process / positive regulation of MAPK cascade / mitochondrial matrix / response to xenobiotic stimulus / positive regulation of apoptotic process / copper ion binding / neuronal cell body / apoptotic process / protein-containing complex / mitochondrion / extracellular space / extracellular exosome / zinc ion binding / extracellular region / nucleoplasm / identical protein binding / nucleus / cytosol / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | helical reconstruction / cryo EM / Resolution: 2.95 Å | ||||||||||||
![]() | Wang LQ / Ma YY / Yuan HY / Zhao K / Zhang MY / Wang Q / Huang X / Xu WC / Chen J / Li D ...Wang LQ / Ma YY / Yuan HY / Zhao K / Zhang MY / Wang Q / Huang X / Xu WC / Chen J / Li D / Zhang DL / Zou LY / Yin P / Liu C / Liang Y | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion. Authors: Li-Qiang Wang / Yeyang Ma / Han-Ye Yuan / Kun Zhao / Mu-Ya Zhang / Qiang Wang / Xi Huang / Wen-Chang Xu / Bin Dai / Jie Chen / Dan Li / Delin Zhang / Zhengzhi Wang / Liangyu Zou / Ping Yin / ...Authors: Li-Qiang Wang / Yeyang Ma / Han-Ye Yuan / Kun Zhao / Mu-Ya Zhang / Qiang Wang / Xi Huang / Wen-Chang Xu / Bin Dai / Jie Chen / Dan Li / Delin Zhang / Zhengzhi Wang / Liangyu Zou / Ping Yin / Cong Liu / Yi Liang / ![]() Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share ...Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3-55) and C-terminal segment (residues 86-153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states. | ||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 10.9 KB 10.9 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.3 KB | Display | ![]() |
Images | ![]() | 100.7 KB | ||
Filedesc metadata | ![]() | 5.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vzfMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | The cryo-EM map of SOD1 fibril. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Human SOD1 amyloid fibril
Entire | Name: Human SOD1 amyloid fibril |
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Components |
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-Supramolecule #1: Human SOD1 amyloid fibril
Supramolecule | Name: Human SOD1 amyloid fibril / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Superoxide dismutase [Cu-Zn]
Macromolecule | Name: Superoxide dismutase [Cu-Zn] / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO / EC number: superoxide dismutase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 15.958757 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MATKAVCVLK GDGPVQGIIN FEQKESNGPV KVWGSIKGLT EGLHGFHVHE FGDNTAGCTS AGPHFNPLSR KHGGPKDEER HVGDLGNVT ADKDGVADVS IEDSVISLSG DHCIIGRTLV VHEKADDLGK GGNEESTKTG NAGSRLACGV IGIAQ UniProtKB: Superoxide dismutase [Cu-Zn] |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | helical array |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |