Human microtubule-associated protein tau (MAPT) predicted structure via E8 lattice topological optimization

Protein target This record contains the predicted 3D structure of human microtubule-associated protein tau (MAPT / tau protein, UniProt P10636, 758 amino acids, canonical isoform), generated using the E8 Navigator — a symmetry-based, non-data-driven protein folding method.MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEGGRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPAQDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLEFTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPAAAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSSDPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL Biological relevance Tau is a microtubule-associated protein that promotes microtubule assembly and stability, playing a key role in neuronal polarity, axonal transport, and cytoskeletal organization. It is centrally implicated in tauopathies — a group of neurodegenerative disorders including Alzheimer’s disease (where hyperphosphorylated tau aggregates into neurofibrillary tangles), frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. Accurate modeling of tau’s conformational ensemble is essential for understanding aggregation, phosphorylation effects, and therapeutic targeting. Why this is a challenging folding problem Tau is intrinsically disordered and structurally unsolved at full length: Approximately 90% of the protein is intrinsically disordered, with only transient secondary structure in microtubule-binding repeat domains No high-resolution experimental structure exists for any full-length physiological tau isoform (only fragments, aggregated filaments, or pathological paired helical filaments have been solved, e.g. PDB 5O3L, 6MZ9, 6QJQ) AlphaFold and similar tools typically assign very low pLDDT scores (