Geometry based prediction of tau protein sites and motifs associated with misfolding and aggregation.

ABSTRACT: Recent studies of tau proteins point to specific sites or motifs along the protein related to its misfolding and aggregation propensity, which is associated with neurodegenerative diseases of structure-dependent pathology. In this manuscript we employ topology and geometry to analyze the local structure of tau proteins obtained from the Protein Data Bank. Our results show that mathematical topology/geometry of cryo-EM structures alone identify the PGGG motifs, and the PHF6(*) motifs as sites of interest and reveal a geometrical hierarchy of the PGGG motifs that differs for 3R+4R and 4R tauopathies. By employing the Local Topological Free Energy (LTE), we find that progressive supranuclear palsy (PSP) and globular glial tauopathy (GGT) have the highest LTE values around residues 302-305, wh

SUBMITTER: Sugiyama M 

PROVIDER: S-EPMC11937417 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature