Database: EMDB / ID: EMD-33332
|Title||Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-1) Parkinson's disease patient|
|Function / homology|
Function and homology information
negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of hydrogen peroxide catabolic process / positive regulation of SNARE complex assembly ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of hydrogen peroxide catabolic process / positive regulation of SNARE complex assembly / supramolecular fiber / regulation of reactive oxygen species biosynthetic process / regulation of glutamate secretion / negative regulation of chaperone-mediated autophagy / mitochondrial membrane organization / negative regulation of platelet-derived growth factor receptor signaling pathway / negative regulation of transporter activity / regulation of synaptic vesicle recycling / negative regulation of exocytosis / response to iron(II) ion / regulation of norepinephrine uptake / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / regulation of locomotion / SNARE complex assembly / synaptic vesicle priming / positive regulation of inositol phosphate biosynthetic process / dopamine uptake involved in synaptic transmission / negative regulation of histone acetylation / regulation of macrophage activation / synaptic vesicle transport / negative regulation of microtubule polymerization / dynein complex binding / positive regulation of receptor recycling / mitochondrial ATP synthesis coupled electron transport / regulation of dopamine secretion / response to magnesium ion / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / synaptic vesicle exocytosis / cuprous ion binding / positive regulation of endocytosis / positive regulation of exocytosis / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / alpha-tubulin binding / kinesin binding / regulation of presynapse assembly / synaptic vesicle endocytosis / supramolecular fiber organization / negative regulation of serotonin uptake / axon terminus / phospholipid metabolic process / localization / regulation of neuron death / cellular response to epinephrine stimulus / excitatory postsynaptic potential / SNARE binding / inclusion body / adult locomotory behavior / response to interleukin-1 / Hsp70 protein binding / long-term synaptic potentiation / positive regulation of release of sequestered calcium ion into cytosol / fatty acid metabolic process / synapse organization / cellular response to copper ion / microglial cell activation / regulation of long-term neuronal synaptic plasticity / regulation of transmembrane transporter activity / ferrous iron binding / positive regulation of protein serine/threonine kinase activity / protein destabilization / phospholipid binding / protein tetramerization / synaptic vesicle membrane / negative regulation of neuron death / tau protein binding / receptor internalization / phosphoprotein binding / negative regulation of protein kinase activity / positive regulation of inflammatory response / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron death / activation of cysteine-type endopeptidase activity involved in apoptotic process / cell cortex / actin cytoskeleton / cellular response to oxidative stress / growth cone / actin binding / postsynapse / chemical synaptic transmission / histone binding / neuron apoptotic process / positive regulation of peptidyl-serine phosphorylation / response to lipopolysaccharide / amyloid fibril formation / negative regulation of neuron apoptotic process / lysosome / molecular adaptor activity
Similarity search - Function
Synuclein / Alpha-synuclein / Synuclein
Similarity search - Domain/homology
Similarity search - Component
|Biological species||Homo sapiens (human)|
|Method||helical reconstruction / cryo EM / Resolution: 3.0 Å|
|Authors||Fan Y / Sun YP / Wang J / Liu C|
|Funding support|| China, 7 items |
|Citation||Journal: Structure / Year: 2023|
Title: Conformational change of α-synuclein fibrils in cerebrospinal fluid from different clinical phases of Parkinson's disease.
Authors: Yun Fan / Yunpeng Sun / Wenbo Yu / Youqi Tao / Wencheng Xia / Yiqi Liu / Qinyue Zhao / Yilin Tang / Yimin Sun / Fengtao Liu / Qin Cao / Jianjun Wu / Cong Liu / Jian Wang / Dan Li /
Abstract: α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease ...α-Synuclein (α-syn) has been shown to form various conformational fibrils associated with different synucleinopathies. But whether the conformation of α-syn fibrils changes during disease progression is unclear. Here, we amplified α-syn aggregates from the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) staged in preclinical PD (pre-PD), middle- to late-stage PD (mid-PD), and late-stage PD (late-PD). Our results show that α-syn fibrils derived from the late-PD patient are most potent in inducing endogenous α-syn aggregation in primary neurons, followed by the mid-PD and pre-PD fibrils. By using cryo-electron microscopy, we further determined the high-resolution structures of the CSF-amplified fibrils. The structures exhibit remarkable differences in a minor but significant population of conformational species in different staged samples. Our work demonstrates structural and pathological differences between α-syn fibrils derived from PD patients at a spectrum of clinical stages, which suggests potential conformational transition of α-syn fibrils during the progression of PD.
Downloads & links
|File||Download / File: emd_33332.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.06 Å|
|Symmetry||Space group: 1|
-Half map: #2
|Projections & Slices|
-Half map: #1
-Entire : Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal ...
|Entire||Name: Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-1) Parkinson's disease patient|
-Supramolecule #1: Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal ...
|Supramolecule||Name: Minor polymorph inalpha-synuclein fibril seeded by cerebrospinal fluid from a mid-to-late stage (mid-PD-1) Parkinson's disease patient|
type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all
|Source (natural)||Organism: Homo sapiens (human)|
-Macromolecule #1: Alpha-synuclein
|Macromolecule||Name: Alpha-synuclein / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO|
|Source (natural)||Organism: Homo sapiens (human)|
|Molecular weight||Theoretical: 14.476108 KDa|
|Recombinant expression||Organism: Escherichia coli (E. coli)|
MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIA AATGFVKKDQ LGKNEEGAPQ EGILEDMPVD PDNEAYEMPS EEGYQDYEPE A
|Vitrification||Cryogen name: ETHANE|
|Microscope||FEI TITAN KRIOS|
|Electron beam||Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN|
|Electron optics||Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm|
|Image recording||Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2|
Model: Titan Krios / Image courtesy: FEI Company
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