Identification of Ultramodified
Proteins Using Top-Down
Tandem Mass Spectra
- Publication date
- Publisher
Abstract
Post-translational
modifications (PTMs) play an important role
in various biological processes through changing protein structure
and function. Some ultramodified proteins (like histones) have multiple
PTMs forming PTM patterns that define the functionality of a protein.
While bottom-up mass spectrometry (MS) has been successful in identifying
individual PTMs within short peptides, it is unable to identify PTM
patterns spreading along entire proteins in a coordinated fashion.
In contrast, top-down MS analyzes intact proteins and reveals PTM
patterns along the entire proteins. However, while recent advances
in instrumentation have made top-down MS accessible to many laboratories,
most computational tools for top-down MS focus on proteins with few
PTMs and are unable to identify complex PTM patterns. We propose a
new algorithm, MS-Align-E, that identifies both expected and unexpected
PTMs in ultramodified proteins. We demonstrate that MS-Align-E identifies
many proteoforms of histone H4 and benchmark it against the currently
accepted software tools