Structural mapping techniques distinguish the surfaces of fibrillar 1N3R and 1N4R human tau
| العنوان: | Structural mapping techniques distinguish the surfaces of fibrillar 1N3R and 1N4R human tau |
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| المؤلفون: | Virginie Redeker, Karine Madiona, Ronald Melki, Emilie Caroux |
| المساهمون: | Centre National de la Recherche Scientifique (CNRS), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ANR-17-JPCD-0005,Protest-70,Protecting protein homeostasis in synucleinopathies and tauopathies by modulating the Hsp70/co-chaperone network(2017), ANR-17-JPCD-0002,TransPathND,Intraneuronal transport-related pathways across neurodegenerative diseases(2017), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB) |
| المصدر: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2021, 297, pp.101252. ⟨10.1016/j.jbc.2021.101252⟩ The Journal of Biological Chemistry Journal of Biological Chemistry, 2021, 297, pp.101252. ⟨10.1016/j.jbc.2021.101252⟩ |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | PiD, Pick's disease, Cryo-electron microscopy, Pronase, Biochemistry, PVDF, polyvinylidene difluoride, 0302 clinical medicine, Protein structure, MS2, fragmentation mass spectrum, N-TOP, N-terminal-oriented proteomics, cryo-EM, cryo-electron microscopy, SDS-PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, mass spectrometry, MALDI-TOF-TOF, matrix assisted laser desorption/ionization-time-of-flight-time-of-flight, chemistry.chemical_classification, 0303 health sciences, CID, collision-Induced dissociation, medicine.diagnostic_test, Chemistry, TMPP(, N-succinimidyloxycarbonylmethyl)-tris(2,4,6-trimethoxyphenyl)-phosphonium, DTT, 1,4-dithiotheritol, NHS-biotin, N-hydroxysulfosuccinimide biotin, Amino acid, PSP, progressive supranuclear palsy, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], AD, Alzheimer's disease, Research Article, CBD, corticobasal degeneration, AGD, argyrophilic grain disease, FDR, false discovery rate, Proteolysis, tau fibrils, tau Proteins, macromolecular substances, Fibril, Peptide Mapping, TFA, trifluoroacetic acid, 03 medical and health sciences, Protein Aggregates, Protein Domains, PBS, phosphate buffered saline, protein conformation, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, TEM, transmission electron microscopy, Molecular Biology, TD, tangle disease, 030304 developmental biology, htau, human tau, nanoLC-MS/MS, nanoflow liquid chromatography combined to tandem mass spectrometry bromide, tauopathies, Alternative splicing, Cell Biology, medicine.disease, structural proteomics, MS, mass spectrometry, chemical surface modification, Biophysics, AEBSF, 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, Pick's disease, 030217 neurology & neurosurgery, limited proteolysis |
| الوصف: | International audience; The rigid core of intracellular tau filaments from Alzheimer’s disease (AD), Pick’s disease (PiD), and Corticobasal disease (CBD) brains has been shown to differ in their cryo-EM atomic structure. Despite providing critical information on the intimate arrangement of a fraction of htau molecule within the fibrillar scaffold, the cryo-EM studies neither yield a complete picture of tau fibrillar assemblies structure nor contribute insights into the surfaces that define their interactions with numerous cellular components. Here, using proteomic approaches such as proteolysis and molecular covalent painting, we mapped the exposed amino acid stretches at the surface and those constituting the fibrillar core of in vitro-assembled fibrils of human htau containing one N-terminal domain and three (1N3R) or four (1N4R) C-terminal microtubule-binding repeat domains as a result of alternative splicing. Using limited proteolysis, we identified the proteolytic fragments composing the molecular “bar-code” for each type of fibril. Our results are in agreement with structural data reported for filamentous tau from AD, PiD, and CBD cases predigested with the protease pronase. Finally, we report two amino acid stretches, exposed to the solvent in 1N4R not in 1N3R htau, which distinguish the surfaces of these two kinds of fibrils. Our findings open new perspectives for the design of highly specific ligands with diagnostic and therapeutic potential. |
| اللغة: | English |
| تدمد: | 0021-9258 1083-351X |
| DOI: | 10.1016/j.jbc.2021.101252⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7fb73365cfdfb93b7855667803503848 https://hal-cea.archives-ouvertes.fr/cea-03384553 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7fb73365cfdfb93b7855667803503848 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219258 1083351X |
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| DOI: | 10.1016/j.jbc.2021.101252⟩ |