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

ABSTRACT: Intrinsically disordered proteins (IDPs), such as Tau and phosphorylated Tau (pTau), pose challenges for structural analysis using traditional methods like X-ray crystallography or cryo-EM. However, alternative approaches can still provide insights into their three-dimensional organization at moderate spatial resolution. One such method is cross-linking mass spectrometry (XL-MS), which has become a valuable tool for studying protein structures in solution. The data files deposited here were generated using a novel XL-MS-based method designed to analyze the folding behavior of IDPs. This method constructs weighted interaction networks from cross-linked residue pairs without relying on predefined secondary structure models. Structural differences between protein conformations are assessed by comparing the organization of loop structures within these networks. Validation using bovine serum albumin (BSA) in both native and denatured states indicates that at least 500 cross-links—requiring 5–10 replicate measurements—are necessary for reliable detection of structural changes. Leave-one-out analysis further confirms that these structural transitions are global, emphasizing the need for comprehensive cross-link datasets. Applied to Tau and pTau during arachidonic acid-induced aggregation, the method reveals distinct patterns of structural evolution between the two proteins. The corresponding XL-MS datasets are available here.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Alzheimer's Disease

SUBMITTER: Cristian Arsene  

LAB HEAD: Cristian Arsene

PROVIDER: PXD067659 | Pride | 2026-01-06

REPOSITORIES: Pride