Global Structure of the Intrinsically Disordered Protein Tau Emerges from Its Local Structure.

ABSTRACT: The paradigmatic disordered protein tau plays an important role in neuronal function and neurodegenerative diseases. To disentangle the factors controlling the balance between functional and disease-associated conformational states, we build a structural ensemble of the tau K18 fragment containing the four pseudorepeat domains involved in both microtubule binding and amyloid fibril formation. We assemble 129-residue-long tau K18 chains with atomic detail from an extensive fragment library constructed with molecular dynamics simulations. We introduce a reweighted hierarchical chain growth (RHCG) algorithm that integrates experimental data reporting on the local structure into the assembly process in a systematic manner. By combining Bayesian ensemble refinement with importance sampling, we

SUBMITTER: Stelzl LS 

PROVIDER: S-EPMC8970000 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature