Higher-order structural interrogation of antibodies using middle-down hydrogen/deuterium exchange mass spectrometry.

ABSTRACT: Although X-ray crystallography is the "gold standard" method for protein higher-order structure analysis, the challenges of antibody crystallization and the time-consuming data analysis involved make this technique unsuitable for routine structural studies of antibodies. In addition, crystallography cannot be used for the structural characterization of an antibody in solution, under conditions where antibody drugs are active. Intact antibodies are also too large and too complex for NMR. Top-down mass spectrometry coupled to hydrogen/deuterium exchange (HDX) is a powerful tool for high-resolution protein structural characterization, but its success declines rapidly as protein size increases. Here we report for the first time a new hybrid "middle-down" HDX approach that overcomes this limita

SUBMITTER: Pan J 

PROVIDER: S-EPMC5975933 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature