8A9L | pdb_00008a9l

Cryo-EM structure of alpha-synuclein filaments from Parkinson's disease and dementia with Lewy bodies

External Resource: Annotation

Domain Annotation: ECOD Classification
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Synuclein	e8a9lA1	A: extended segments	X: Alpha-synuclein (From Topology)	H: Alpha-synuclein (From Topology)	T: Alpha-synuclein	F: Synuclein	ECOD (1.6)

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Alpha-synuclein	protein binding binding histone binding phospholipid binding lipid binding cytoskeletal protein binding tubulin binding alpha-tubulin binding oxidoreductase activity catalytic activity cation binding ion binding calcium ion binding metal ion binding protein binding binding histone binding phospholipid binding lipid binding cytoskeletal protein binding tubulin binding alpha-tubulin binding oxidoreductase activity catalytic activity cation binding ion binding calcium ion binding metal ion binding small molecule binding kinesin binding enzyme regulator activity cysteine-type endopeptidase inhibitor activity involved in apoptotic process molecular function regulator activity cysteine-type endopeptidase regulator activity involved in apoptotic process magnesium ion binding cuprous ion binding transition metal ion binding copper ion binding iron ion binding ferrous iron binding DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding nucleic acid binding transcription regulatory region nucleic acid binding phosphoprotein binding tau protein binding molecular adaptor activity identical protein binding catalytic activity, acting on a protein kinase activity protein kinase activity enzyme inhibitor activity transferase activity protein kinase regulator activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein kinase inhibitor activity molecular function inhibitor activity kinase inhibitor activity kinase regulator activity Hsp70 protein binding protein-folding chaperone binding heat shock protein binding SNARE binding actin binding zinc ion binding protein-containing complex binding dynein complex binding	response to stimulus response to chemical response to xenobiotic stimulus neutral lipid metabolic process primary metabolic process metabolic process cellular process lipid metabolic process cellular response to stimulus regulation of cellular process negative regulation of signaling signaling negative regulation of biological process regulation of signal transduction response to stimulus response to chemical response to xenobiotic stimulus neutral lipid metabolic process primary metabolic process metabolic process cellular process lipid metabolic process cellular response to stimulus regulation of cellular process negative regulation of signaling signaling negative regulation of biological process regulation of signal transduction regulation of platelet-derived growth factor receptor signaling pathway negative regulation of cell communication cell surface receptor protein tyrosine kinase signaling pathway cell communication negative regulation of cellular process signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling regulation of biological process cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of platelet-derived growth factor receptor signaling pathway biological regulation platelet-derived growth factor receptor signaling pathway negative regulation of signal transduction regulation of response to stimulus regulation of cell communication membrane organization protein-containing complex organization transport membrane fusion organelle membrane fusion establishment of localization vesicle-mediated transport cellular component organization cellular component biogenesis vesicle organization organelle fusion localization organelle organization cellular component assembly protein-containing complex assembly SNARE complex assembly cellular component organization or biogenesis vesicle fusion monoamine transport import into cell regulation of localization cellular localization regulation of catecholamine uptake involved in synaptic transmission negative regulation of catecholamine uptake involved in synaptic transmission nitrogen compound transport negative regulation of amine transport negative regulation of transport organic hydroxy compound transport negative regulation of neurotransmitter transport dopamine transport catecholamine uptake dopamine uptake involved in synaptic transmission synaptic signaling catecholamine transport establishment of localization in cell regulation of dopamine uptake involved in synaptic transmission neurotransmitter reuptake regulation of neurotransmitter uptake trans-synaptic signaling regulation of transport catecholamine uptake involved in synaptic transmission regulation of neurotransmitter transport cell-cell signaling neurotransmitter transport negative regulation of neurotransmitter uptake chemical synaptic transmission amine transport anterograde trans-synaptic signaling neurotransmitter uptake regulation of amine transport negative regulation of dopamine uptake involved in synaptic transmission synaptic transmission, dopaminergic dopamine uptake negative regulation of monooxygenase activity regulation of molecular function regulation of catalytic activity negative regulation of oxidoreductase activity negative regulation of molecular function negative regulation of catalytic activity regulation of oxidoreductase activity vesicle localization establishment of organelle localization establishment of vesicle localization organelle localization synaptic vesicle localization synaptic vesicle transport positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of biological process regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process positive regulation of cellular process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process regulation of macromolecule metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation macromolecule metabolic process regulation of metabolic process response to iron(II) ion response to metal ion response to iron ion response to oxidative stress cellular response to chemical stimulus cellular response to stress response to stress cellular response to oxidative stress cellular response to chemical stress norepinephrine transport negative regulation of norepinephrine uptake organic cation transport regulation of norepinephrine uptake norepinephrine uptake dopamine metabolic process catechol-containing compound metabolic process amine metabolic process biogenic amine biosynthetic process biosynthetic process catecholamine metabolic process amine biosynthetic process dopamine biosynthetic process phenol-containing compound metabolic process catecholamine biosynthetic process phenol-containing compound biosynthetic process catechol-containing compound biosynthetic process biogenic amine metabolic process biological process involved in interspecies interaction between organisms immune response response to other organism defense response response to type II interferon response to cytokine defense response to symbiont response to external stimulus response to biotic stimulus response to peptide immune system process defense response to other organism innate immune response response to external biotic stimulus reactive oxygen species biosynthetic process regulation of biosynthetic process reactive oxygen species metabolic process regulation of reactive oxygen species biosynthetic process regulation of reactive oxygen species metabolic process regulation of transferase activity positive regulation of protein serine/threonine kinase activity positive regulation of molecular function positive regulation of protein kinase activity positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity positive regulation of kinase activity regulation of kinase activity regulation of protein serine/threonine kinase activity aerobic respiration cellular respiration oxidative phosphorylation energy derivation by oxidation of organic compounds ATP synthesis coupled electron transport electron transport chain generation of precursor metabolites and energy respiratory electron transport chain mitochondrial ATP synthesis coupled electron transport regulated exocytosis synaptic vesicle priming synaptic vesicle cycle synaptic vesicle exocytosis vesicle-mediated transport in synapse secretion by cell signal release neurotransmitter secretion secretion export from cell signal release from synapse exocytosis exocytic process RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process multicellular organismal process cell activation myeloid leukocyte activation leukocyte activation macrophage activation leukocyte activation involved in inflammatory response microglial cell activation inflammatory response glial cell activation neuroinflammatory response regulation of glutamate secretion regulation of secretion by cell regulation of amino acid transport glutamate secretion organic anion transport carboxylic acid transport regulation of secretion organic acid transport amino acid transport acidic amino acid transport regulation of organic acid transport dicarboxylic acid transport phospholipid metabolic process organophosphate metabolic process regulation of cytoskeleton organization regulation of microtubule polymerization or depolymerization regulation of cellular component organization microtubule cytoskeleton organization regulation of protein-containing complex assembly microtubule polymerization or depolymerization negative regulation of protein polymerization negative regulation of supramolecular fiber organization protein polymerization negative regulation of cellular component organization negative regulation of microtubule polymerization or depolymerization negative regulation of cytoskeleton organization regulation of microtubule-based process negative regulation of microtubule polymerization microtubule polymerization regulation of cellular component biogenesis regulation of organelle organization negative regulation of protein-containing complex assembly negative regulation of organelle organization regulation of protein polymerization regulation of microtubule polymerization regulation of supramolecular fiber organization microtubule-based process supramolecular fiber organization cytoskeleton organization regulation of microtubule cytoskeleton organization regulation of transmembrane transporter activity regulation of transporter activity transmembrane transport regulation of transmembrane transport negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death positive regulation of secretion by cell positive regulation of exocytosis positive regulation of secretion regulation of vesicle-mediated transport positive regulation of transport regulation of exocytosis amyloid fibril formation regulation of catecholamine secretion dopamine secretion catecholamine secretion regulation of dopamine secretion positive regulation of organelle organization positive regulation of cellular component organization regulation of vesicle fusion positive regulation of protein-containing complex assembly positive regulation of SNARE complex assembly positive regulation of cellular component biogenesis regulation of SNARE complex assembly positive regulation of vesicle fusion cell junction organization synapse organization response to epinephrine cellular response to epinephrine stimulus fatty acid metabolic process oxoacid metabolic process carboxylic acid metabolic process small molecule metabolic process monocarboxylic acid metabolic process organic acid metabolic process regulation of postsynaptic membrane potential system process chemical synaptic transmission, postsynaptic regulation of biological quality nervous system process excitatory postsynaptic potential regulation of membrane potential aerobic electron transport chain negative regulation of cellular respiration regulation of generation of precursor metabolites and energy regulation of cellular respiration regulation of mitochondrial ATP synthesis coupled electron transport negative regulation of oxidative phosphorylation negative regulation of mitochondrial electron transport, NADH to ubiquinone mitochondrial electron transport, NADH to ubiquinone regulation of aerobic respiration regulation of mitochondrial electron transport, NADH to ubiquinone regulation of oxidative phosphorylation negative regulation of mitochondrial ATP synthesis coupled electron transport neuron apoptotic process regulation of calcium ion transport positive regulation of cation transmembrane transport positive regulation of calcium ion transport intracellular calcium ion homeostasis calcium ion transport positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport monoatomic cation homeostasis monoatomic cation transport intracellular monoatomic ion homeostasis regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport inorganic cation transmembrane transport maintenance of location release of sequestered calcium ion into cytosol chemical homeostasis inorganic ion homeostasis homeostatic process monoatomic ion transmembrane transport calcium ion homeostasis regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport intracellular monoatomic cation homeostasis monoatomic ion homeostasis positive regulation of calcium ion transmembrane transport positive regulation of transmembrane transport monoatomic ion transport intracellular chemical homeostasis positive regulation of release of sequestered calcium ion into cytosol regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol sequestering of calcium ion cellular homeostasis regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport serotonin uptake regulation of serotonin uptake serotonin transport negative regulation of serotonin uptake response to lipid response to oxygen-containing compound response to lipopolysaccharide response to bacterium response to molecule of bacterial origin positive regulation of endocytosis endocytosis regulation of endocytosis negative regulation of secretion negative regulation of exocytosis negative regulation of secretion by cell regulation of phospholipase activity regulation of hydrolase activity regulation of defense response regulation of response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stress positive regulation of defense response protein destabilization regulation of protein stability receptor internalization receptor-mediated endocytosis protein complex oligomerization protein tetramerization positive regulation of programmed cell death positive regulation of apoptotic process negative regulation of thrombin-activated receptor signaling pathway negative regulation of G protein-coupled receptor signaling pathway thrombin-activated receptor signaling pathway regulation of G protein-coupled receptor signaling pathway regulation of thrombin-activated receptor signaling pathway G protein-coupled receptor signaling pathway regulation of macrophage activation regulation of leukocyte activation regulation of cell activation regulation of immune system process regulation of multicellular organismal process regulation of neuronal synaptic plasticity regulation of synaptic plasticity regulation of long-term neuronal synaptic plasticity modulation of chemical synaptic transmission regulation of trans-synaptic signaling negative regulation of phosphate metabolic process negative regulation of kinase activity negative regulation of transferase activity negative regulation of protein modification process negative regulation of protein metabolic process negative regulation of protein kinase activity negative regulation of protein phosphorylation negative regulation of phosphorus metabolic process negative regulation of phosphorylation positive regulation of hydrogen peroxide catabolic process catabolic process hydrogen peroxide metabolic process regulation of catabolic process regulation of hydrogen peroxide catabolic process positive regulation of reactive oxygen species metabolic process positive regulation of catabolic process regulation of hydrogen peroxide metabolic process positive regulation of hydrogen peroxide metabolic process hydrogen peroxide catabolic process mitochondrial membrane organization mitochondrion organization positive regulation of peroxidase activity positive regulation of glutathione peroxidase activity positive regulation of oxidoreductase activity regulation of glutathione peroxidase activity regulation of inositol phosphate biosynthetic process alcohol metabolic process inositol phosphate metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process polyol biosynthetic process regulation of carbohydrate metabolic process carbohydrate metabolic process polyol metabolic process regulation of alcohol biosynthetic process small molecule biosynthetic process carbohydrate biosynthetic process positive regulation of inositol phosphate biosynthetic process organophosphate biosynthetic process inositol phosphate biosynthetic process alcohol biosynthetic process positive regulation of carbohydrate metabolic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process positive regulation of alcohol biosynthetic process autophagy regulation of autophagy macromolecule catabolic process negative regulation of protein catabolic process chaperone-mediated autophagy process utilizing autophagic mechanism negative regulation of catabolic process protein catabolic process regulation of chaperone-mediated autophagy negative regulation of chaperone-mediated autophagy negative regulation of autophagy regulation of protein catabolic process synaptic vesicle endocytosis presynaptic endocytosis synaptic vesicle recycling adult locomotory behavior behavior adult behavior locomotory behavior regulation of presynapse assembly multicellular organism development regulation of presynapse organization cell junction assembly anatomical structure development regulation of synapse structure or activity regulation of synapse assembly system development developmental process presynapse organization nervous system development regulation of cell junction assembly regulation of synapse organization synapse assembly presynapse assembly response to interleukin-1 positive regulation of protein localization to cell periphery protein localization protein localization to cell periphery regulation of protein localization regulation of protein localization to cell periphery regulation of cellular localization cellular macromolecule localization macromolecule localization positive regulation of protein localization regulation of synaptic vesicle recycling negative regulation of neuron apoptotic process regulation of neuron apoptotic process regulation of receptor recycling receptor recycling receptor metabolic process positive regulation of receptor recycling positive regulation of signaling regulation of acyl-CoA biosynthetic process regulation of amide metabolic process regulation of lipid metabolic process regulation of sulfur metabolic process sulfur compound metabolic process thioester metabolic process nucleoside phosphate metabolic process amide biosynthetic process regulation of ketone metabolic process sulfur compound biosynthetic process nucleoside phosphate biosynthetic process regulation of fatty acid metabolic process thioester biosynthetic process ketone metabolic process acyl-CoA metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process amide metabolic process purine-containing compound metabolic process response to copper ion cellular response to metal ion cellular response to copper ion positive regulation of cell communication positive regulation of neurotransmitter secretion positive regulation of neurotransmitter transport positive regulation of synaptic transmission regulation of neurotransmitter secretion negative regulation of transporter activity long-term synaptic potentiation regulation of locomotion locomotion response to magnesium ion	intracellular organelle cellular anatomical structure intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol inclusion body extracellular region extracellular space supramolecular fiber intracellular organelle cellular anatomical structure intracellular anatomical structure cytoskeleton organelle membraneless organelle intracellular membraneless organelle actin cytoskeleton cytoplasm cytosol inclusion body extracellular region extracellular space supramolecular fiber supramolecular polymer supramolecular complex cell periphery plasma membrane membrane membrane-bounded organelle lytic vacuole vacuole intracellular membrane-bounded organelle lysosome protein-containing complex perinuclear region of cytoplasm somatodendritic compartment cell body neuronal cell body synapse intracellular vesicle transport vesicle membrane endomembrane system presynapse bounding membrane of organelle cytoplasmic vesicle vesicle membrane synaptic vesicle synaptic vesicle membrane cell junction vesicle transport vesicle exocytic vesicle membrane cytoplasmic vesicle membrane secretory vesicle organelle membrane exocytic vesicle axon cell projection neuron projection plasma membrane bounded cell projection postsynapse mitochondrion cell cortex growth cone distal axon site of polarized growth axon terminus neuron projection terminus nucleus
B	Unknown fragment	-	-	-
C	Unknown fragment	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR001058	Synuclein	Family
A	IPR002460	Alpha-synuclein	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P37840	Parkinson disease Lewy body dementia Gaucher disease autosomal dominant Parkinson disease 4 autosomal dominant Parkinson disease 1 neurodegenerative disease Wilson disease multiple system atrophy Alzheimer disease manganese poisoning amphetamine abuse drug psychosis cocaine abuse Nerve Degeneration cocaine dependence Parkinson disease Lewy body dementia Gaucher disease autosomal dominant Parkinson disease 4 autosomal dominant Parkinson disease 1 neurodegenerative disease Wilson disease multiple system atrophy Alzheimer disease manganese poisoning amphetamine abuse drug psychosis cocaine abuse Nerve Degeneration cocaine dependence parkinsonian-pyramidal syndrome alcohol abuse meningococcal meningitis endometritis primitive neuroectodermal tumor autosomal recessive juvenile Parkinson disease 2 exocrine pancreatic carcinoma intellectual disability bacterial pneumonia oligodendroglioma breast cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia actinic keratosis chronic obstructive pulmonary disease parkinsonian disorder late-onset Parkinson disease sleep-wake disorder lung adenocarcinoma malignant colon neoplasm Pick disease amyloidosis malignant mesothelioma astrocytic tumor toxic encephalopathy vitamin A deficiency medulloblastoma Huntington disease prion disease psoriasis invasive ductal breast carcinoma osteosarcoma breast carcinoma glioblastoma acute gonococcal cervicitis lameness, non-human animal cutaneous lupus erythematosus lung cancer malignant ependymoma pilocytic astrocytoma amyotrophic lateral sclerosis malignant pancreatic neoplasm head and neck cancer transitional cell carcinoma progressive supranuclear palsy bacterial arthritis bacterial meningitis non-small cell lung carcinoma ovarian cancer rhinoscleroma chancroid acute gonococcal endometritis Sjogren syndrome large cell medulloblastoma gonorrhea major depressive disorder dementia streptococcal meningitis malignant glioma arthropathy atypical teratoid rhabdoid tumor tuberculosis

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.