Cross-linking mass spectrometry for structure analysis of the intrinsically disordered Tau and phosphorylated Tau protein.

ABSTRACT: We present a novel method for analyzing the folding of intrinsically disordered proteins (IDPs), such as Tau and phosphorylated Tau (pTau), in solution. Using cross-linking mass spectrometry (XL-MS) combined with a new downstream analysis framework, we construct weighted interaction networks from cross-link-derived residue pairs without relying on predefined secondary structure assumptions. Structural differences between protein conformations are quantified by comparing the organization of loop structures within their cross-link networks. Validation with bovine serum albumin (BSA) in native and denatured states shows that at least 500 cross-links-requiring 5-10 replicate measurements-are needed for reliable detection of structural divergence. Leave-one-out analysis confirms that structural

SUBMITTER: Arsene C 

PROVIDER: S-EPMC12826526 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature