Structural Characterization of Missense Mutations Using High Resolution Mass Spectrometry: A Case Study of the Parkinson's-Related Protein, DJ-1.

ABSTRACT: Missense mutations that lead to the expression of mutant proteins carrying single amino acid substitutions are the cause of numerous diseases. Unlike gene lesions, insertions, deletions, nonsense mutations, or modified RNA splicing, which affect the length of a polypeptide, or determine whether a polypeptide is translated at all, missense mutations exert more subtle effects on protein structure, which are often difficult to evaluate. Here, we took advantage of the spectral resolution afforded by the EMR Orbitrap platform, to generate a mass spectrometry-based approach relying on simultaneous measurements of the wild-type protein and the missense variants. This approach not only considerably shortens the analysis time due to the concurrent acquisition but, more importantly, enables direct c

SUBMITTER: Ben-Nissan G 

PROVIDER: S-EPMC5152731 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature