Structural mapping of the surfaces of fibrillar 1N3R and 1N4R human tau

ABSTRACT: The structural characterization of pathogenic tau filaments that accumulate in tauopathies, including Alzheimer disease, is key for understanding their pathogenic function and identify the structural determinants of distinct tau filaments involved in distinct tauopathies. Fibrillar tau surfaces play a crucial role in tau fibrils interaction with various protein partners and binding to neurons, a key step for their prion-like propagation propensity. In order to identify the amino acid residues stretches that are exposed and those that are not exposed to the solvent within tau fibrils, we used structural proteomic approaches: proteolysis and molecular covalent surface painting using NHS-Biotin followed by MS-based analysis of the proteolytic products. We compared the solvent accessible amino acid residues on the surface of htau proteins upon assembly of 1N3R and 1N4R human htau monomers into fibrils in vitro. We mapped the amino acid segments exposed or unexposed on the surface of htau fibrils by determining the accessibility GluC enzyme and NHS-biotin followed by proteolysis. The proteolytic peptides were analyzed by nanoLC-MSMS and processed using Mascot for their identification and PeakView for intensity extraction of labeled and unlabeled proteolytic peptides.

INSTRUMENT(S): TripleTOF 4600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Tauopathy,Alzheimer's Disease

SUBMITTER: Virginie Redeker  

LAB HEAD: Virginie REDEKER

PROVIDER: PXD027403 | Pride | 2022-02-17

REPOSITORIES: Pride