{"database":"MassIVE","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://massive-ftp.ucsd.edu/x01/MSV000080692/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":0,"searchCount":0},"additional":{"submitter":["Siu-Kwan Sze"],"full_dataset_link":["https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=dd1b1375e4c4455098c8f3bb310e2889"],"submitter_email":["sksze@ntu.edu.sg"],"sample_protocol":[""],"repository":["MassIVE"],"file_size":["106"],"ptm_modification":["MOD:00400 - \"A protein modification that effectively replaces a carboxamido group with a carboxyl group, with both a gain of oxygen and loss of a nitrogen and a hydrogen.\""],"data_protocol":[""],"omics_type":["Proteomics"],"instrument_platform":["Q Exactive"],"species":["Homo Sapiens (ncbitaxon:9606)"],"submitter_affiliation":["Nanyang Technological University"],"pubmed_abstract":["<h4>Background</h4>Aggregation of malformed proteins is a key feature of many neurodegenerative diseases, but the mechanisms that drive proteinopathy in the brain are poorly understood. We aimed to characterize aggregated proteins in human brain tissues affected by dementia.<h4>Results</h4>To characterize amyloidal plaque purified from post-mortem brain tissue of dementia patient, we applied ultracentrifugation-electrostatic repulsion hydrophilic interaction chromatography (UC-ERLIC) coupled mass spectrometry-based proteomics technologies. Proteomics profiling of both soluble and aggregated amyloidal plaque demonstrated significant enrichment and deamidation of S100A9, ferritin, hemoglobin subunits, creatine kinase and collagen protein among the aggregated brain proteins. Amyloidal plaques were enriched in the deamidated variant of protein S100A9, and structural analysis indicated that both the low- and high-affinity calcium binding motifs of S100A9 were deamidated exclusively in the aggregated fraction, suggesting altered charge state and function of this protein in brain tissues affected by dementia. The multiple deamidated residues of S100A9 predicts introduction of negative charge that alter Ca(++) binding, suggesting increased capacity to form pathological aggregates in the brain.<h4>Conclusion</h4>UC-coupled proteomics revealed that brain amyloidal plaques are enriched in deamidated proteins, and suggested that altered charge state and calcium-binding capacity of S100A9 may enhance protein aggregation and promote neurodegeneration in the human brain."],"pubmed_title":["Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues."],"pubmed_authors":["Adav Sunil S SS, Gallart-Palau Xavier X, Tan Kok Hian KH, Lim Sai Kiang SK, Tam James P JP, Sze Siu Kwan SK"],"pubmed_title_synonyms":["the brain, Senile, suprasegmental structures, human being, Tissue., protein complex, Amentias, Modern, Proteins, Gene, protein, protein-containing complex, encephalon, Human, protein polypeptide chains, systemic amyloidosis, Progressive dementia, native protein, natural protein, polypeptide chain, Homo sapiens, Protein, Gene Products, amyloid, synganglion, dementia (disease), protein aggregate, dementia, Paranoid Dementia, Man, amyloid disease, Senile Paranoid Dementias, Dementia, Senile Paranoid Dementia, amyloidosis, amyloidoses, Man (Taxonomy), Paranoid Dementias, Amentia, Encephalon, amyloidosis (disease), Dementias, Familial, proteins, suprasegmental levels of nervous system, human, Protein Gene Products, Familial Dementia, Gene Proteins, Senile Paranoid, Modern Man, Familial Dementias, progressive, humans, Amyloidoses"],"description_synonyms":["amyloidosis, amyloidoses, protein complex, Proteins, amyloidosis (disease), total expressed protein, Gene, proteins, protein, protein-containing complex, Protein Gene Products, Gene Proteins, protein polypeptide chains, systemic amyloidosis, native protein, natural protein, polypeptide chain, soluble, Protein, Proteomes., Gene Products, amyloid, protein aggregate, amyloid disease, Amyloidoses"],"name_synonyms":["Human, the brain, liquid chromatography tandem mass spectroscopy, LC-MS2, LC/MS/MS, suprasegmental structures, human being, LCMSMS, Man (Taxonomy), Homo sapiens, liquid chromatography-tandem mass spectroscopy, Modern Man, LC-MSMS, Modern, Encephalon, LC-MS/MS, liquid chromatography tandem mass spectrometry, LC-MS-MS., synganglion, suprasegmental levels of nervous system, Man, encephalon, human, humans"],"pubmed_abstract_synonyms":["Forms, deceased, Ferritin, Collagens, Protein folding disease, determination, Amentias, Calcium 40, Neurologic Diseases, Protein Folding Disease, Protein Misfolding Disorder, Neurologic Degenerative Condition, protein, Cardiac Death, ATP Creatine, folding disorders, Neurodegenerative Diseases, protein polypeptide chains, Misfolding disorder, fth1, Protein folding disorder, diseases, Neurologic Disorders, MIF, plif, synganglion, Kinase, Analysis, dementia (disease), Zyderm, protein aggregate, dementia, Paranoid Dementia, IKKg, KEY, Key, Nervous System Degenerative Diseases, Mass Spectrum Analysis, LIAG, calcio, increased, Basic Isoferritin, me75, Degenerative Condition, AW546964, fam:CK, Man (Taxonomy), L1Ag, Analyses, Phosphokinase, Amentia, folding disorder, Microfibril Collagen Hemostat, Tissue, Misfolding diseases, Familial, Subunits, proteins, suprasegmental levels of nervous system, Neurodegenerative Disorder, Phosphocreatine Phosphotransferase, D17Mit170, T1, Misfolding Disease, 60B8Ag, Macro-Creatine Kinase, L1AG, collagen, Degenerative Neurologic Disease, pig15, Protein Misfolding Diseases, Collagen Fleece, Protein Folding Diseases, Neurologic Degenerative Disease, P14, Collagen, Familial Dementias, Misfolding disease, z, Neuro-degenerative disease, Proteinopathies, ATP, 60B8AG, Blood Coagulation Factor IV, Ca, Proteinopathy, Senile, suprasegmental structures, Coagulation, Creatine, ADP, Protein folding disorders, Protein Folding Disorder, Modern, p14, Hemoglobin, Tl3, Tl2, Spectrum Analysis, results, Protein Misfolding, Spectroscopy, DmIKKgamma, Progressive dementia, soluble, dIKK, Kenny, ADP Phosphocreatine, Progressive neurodegenerative disorder, simple tissue, Dysfunction, Misfolding Disorder, Proteostasis Dysfunctions, Dementia, Senile Paranoid Dementia, ferritin, Proteostasis, CGLB, Drives, Degenerative Diseases, Protein Misfolding disorder, MRP14, Encephalon, IKK-gamma, Spectrometry, Dementias, ftn-2, Neurologic Disease, Neurodegenerative disease, Mrp14, human, Encephalon., disease, calcium, DmelCG16910, Patient, Degenerative, ATP:creatine N-phosphotransferase, folding diseases, Protein Misfolding disorders, Collagen Felt, progressive, humans, accessory, Proteostasis Dysfunction, the brain, human being, Peptidomics, Degenerative Neurologic Disorders, alpha-Collagen, Gene, GAGB, Spectrum Analyses, Protein Folding Disorders, protein-containing complex, supernumerary, dIKK-gamma, cerebral degeneration disease, Human, Microfibril, Homo sapiens, polypeptide chain, Dermodress, 20Ca, DmIKK-gamma, Collastat, Factor IV, Gene Products, Mass, Low, dmIKKgamma, IKK[[gamma]], Man, Phosphotransferase, ATP Creatine Phosphotransferase, Senile Paranoid Dementias, Mass Spectroscopy, Ca(0), Calcium-40, Nervous System, ligand, Protein Misfolding diseases, Proteostasis Deficiency, Avitene, Protein folding, fth, Neurodegenerative Disorders, alpha Collagen, Neurologic, Protein Misfolding Disease, Neurologic Degenerative Diseases, IKK, ADP Phosphocreatine Phosphotransferase, Clients, apoferritin, Disorder, Protein Folding, Degenerative Neurologic Diseases, folding disease, Folding Disorder, disorder, Spinal Cord, Chromatographies, Creatine Phosphotransferase, Collagenfleece, Disease, Neurologic Disorder, cou, Protein Misfolding disease, Protein folding diseases, protein complex, Creatine Phosphokinase, Proteins, disorders, function, Kalzium, Protein Misfolding Disorders, encephalon, Client, Misfolding disorders, Degenerative Neurologic Disorder, IKKgamma, MS, CAGB, Lr, native protein, natural protein, Protein, chemical analysis, post-mortem, Collagen Hemostat, Can, background, Macro Creatine Kinase, Death, Mass Spectrum Analyses, Pangen, Basic, Degenerative Conditions, Mass Spectrum, Calcium, Cagb, Paranoid Dementias, Dmikkgamma, increased number, other collagen, Avicon, Neurologic Degenerative Conditions, patient, CFAG, CG16910, Isoferritin, introduction, Protein Gene Products, BEE22, fhc, Familial Dementia, Gene Proteins, present in greater numbers in organism, Coagulation Factor IV, Deficiency, Senile Paranoid, Folding Disease, NIF, Modern Man, Bra, Neurodegenerative Disease, Central Nervous System, assay, fthl6, MAC387"],"citation_count":["0"],"additional_accession":["PXD002516"]},"is_claimable":true,"name":"Human Brain LC-MS/MS","description":"Brian Protein Deamidation Associated with Amyloidosis Revealed by Soluble and Amyloidal Brian Proteome Profiling","dates":{"publication":"Tue Mar 28 19:41:00 BST 2017"},"accession":"MSV000080692","cross_references":{"pubmed":["26892330"]}}