Computationally Driven Top-Down Mass Spectrometry of Ubiquitinated Proteins.

ABSTRACT: Ubiquitination regulates numerous cellular processes through the attachment of polyubiquitin (Ub) chains that vary in linkage type, length, and branching topology. However, current mass spectrometry approaches cannot simultaneously define both the site of ubiquitination and the topology of the attached Ub chain on intact protein substrates. Here, we present the first integrated strategy that enables simultaneous determination of ubiquitin site and chain architecture using top-down mass spectrometry (TD-MS). Central to this approach is UbqTop , a custom computational platform that predicts Ub chain topology from tandem MS (MS²) fragmentation data by utilizing Bayesian-like scoring algorithm. To address the challenge of analyzing complex substrates, we combine this with selecti

SUBMITTER: Shestoperova EI 

PROVIDER: S-EPMC12324172 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature