+Open data
-Basic information
Entry | Database: PDB / ID: 7yk2 | ||||||
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Title | Cryo-EM structure of Apo-alpha-syn fibril | ||||||
Components | Alpha-synuclein | ||||||
Keywords | PROTEIN FIBRIL / amyloid | ||||||
Function / homology | Function and homology information regulation of phospholipase activity / negative regulation of monooxygenase activity / negative regulation of mitochondrial electron transport, NADH to ubiquinone / positive regulation of glutathione peroxidase activity / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process ...regulation of phospholipase activity / negative regulation of monooxygenase activity / negative regulation of mitochondrial electron transport, NADH to ubiquinone / positive regulation of glutathione peroxidase activity / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / negative regulation of transporter activity / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / regulation of reactive oxygen species biosynthetic process / regulation of synaptic vesicle recycling / negative regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / regulation of glutamate secretion / response to iron(II) ion / regulation of norepinephrine uptake / SNARE complex assembly / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / synaptic vesicle priming / regulation of macrophage activation / negative regulation of microtubule polymerization / synaptic vesicle transport / dopamine uptake involved in synaptic transmission / regulation of dopamine secretion / dynein complex binding / positive regulation of receptor recycling / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / cuprous ion binding / response to magnesium ion / positive regulation of exocytosis / synaptic vesicle exocytosis / positive regulation of endocytosis / kinesin binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / mitochondrial ATP synthesis coupled electron transport / synaptic vesicle endocytosis / regulation of presynapse assembly / negative regulation of serotonin uptake / alpha-tubulin binding / phospholipid metabolic process / supramolecular fiber organization / axon terminus / inclusion body / cellular response to copper ion / cellular response to epinephrine stimulus / Hsp70 protein binding / response to interleukin-1 / : / adult locomotory behavior / positive regulation of release of sequestered calcium ion into cytosol / excitatory postsynaptic potential / SNARE binding / fatty acid metabolic process / long-term synaptic potentiation / phosphoprotein binding / protein tetramerization / regulation of transmembrane transporter activity / protein destabilization / negative regulation of protein kinase activity / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / ferrous iron binding / positive regulation of protein serine/threonine kinase activity / tau protein binding / PKR-mediated signaling / receptor internalization / phospholipid binding / : / synaptic vesicle membrane / positive regulation of inflammatory response / actin cytoskeleton / positive regulation of peptidyl-serine phosphorylation / actin binding / cell cortex / cellular response to oxidative stress / histone binding / growth cone / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / postsynapse / response to lipopolysaccharide / amyloid fibril formation / molecular adaptor activity / lysosome / oxidoreductase activity / transcription cis-regulatory region binding / positive regulation of apoptotic process Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.8 Å | ||||||
Authors | Xu, Q.H. / Xia, W.C. / Tao, Y.Q. / Liu, C. | ||||||
Funding support | 1items
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Citation | Journal: J Am Chem Soc / Year: 2023 Title: Conformational Dynamics of an α-Synuclein Fibril upon Receptor Binding Revealed by Insensitive Nuclei Enhanced by Polarization Transfer-Based Solid-State Nuclear Magnetic Resonance and Cryo-Electron Microscopy. Authors: Shengnan Zhang / Juan Li / Qianhui Xu / Wencheng Xia / Youqi Tao / Chaowei Shi / Dan Li / ShengQi Xiang / Cong Liu / Abstract: Many amyloid fibrils associated with neurodegenerative diseases consist of an ordered fibril core (FC) and disordered terminal regions (TRs). The former represents a stable scaffold, while the latter ...Many amyloid fibrils associated with neurodegenerative diseases consist of an ordered fibril core (FC) and disordered terminal regions (TRs). The former represents a stable scaffold, while the latter is rather active in binding with various partners. Current structural studies mainly focus on the ordered FC since the high flexibility of TRs hinders structural characterization. Here, by combining insensitive nuclei enhanced by polarization transfer-based H-detected solid-state NMR and cryo-EM, we explored the intact structure of an α-syn fibril including both FC and TRs and further studied the conformational dynamics of the fibril upon binding to lymphocyte activation gene 3 (LAG3)─a cell surface receptor that is involved in α-syn fibril transmission in brains. We found that both the N- and C-TRs of α-syn are disordered in free fibrils featuring similar conformation ensembles as those in soluble monomers. While in the presence of the D1 domain of LAG3 (L3D1), the C-TR directly binds to L3D1, meanwhile the N-TR folds into a β-strand and further integrates with the FC, which leads to alteration of the overall fibril structure and surface property. Our work reveals synergistic conformational transition of the intrinsically disordered TRs of α-syn, which sheds light on mechanistic understanding of the essential role of TRs in regulating the structure and pathology of amyloid fibrils. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7yk2.cif.gz | 70.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7yk2.ent.gz | 51.3 KB | Display | PDB format |
PDBx/mmJSON format | 7yk2.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7yk2_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7yk2_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | 7yk2_validation.xml.gz | 27 KB | Display | |
Data in CIF | 7yk2_validation.cif.gz | 38.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/yk/7yk2 ftp://data.pdbj.org/pub/pdb/validation_reports/yk/7yk2 | HTTPS FTP |
-Related structure data
Related structure data | 33884MC 7yk8C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 14476.108 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SNCA, NACP, PARK1 / Production host: Escherichia coli K-12 (bacteria) / References: UniProt: P37840 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of Apo-alpha-syn fibril / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
CTF correction | Type: NONE |
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Helical symmerty | Angular rotation/subunit: 179.634 ° / Axial rise/subunit: 2.412 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 53784 / Symmetry type: HELICAL |