3A-O2-1700 PDF
Ionization and Ion Separation Methods Required for the Identification of a Novel Post-translational Modification of α-Dystroglycan
Aberrant O-Man glycosylation of a cell surface glycoprotein, α-dystroglycan (α-DG), causes muscular dystrophies due to failure of binding to extracellular matrix and synaptic proteins, and the [Xyl-GlcA] repeat extending from the phosphorylated O-Man via a putative phosphodiester-linked moiety is involved in this key function of α-DG. Recently, our collaboration team has determined that the moiety is a tandem ribitol-phosphate repeat. A breakthrough was made by MALDI linear TOF MS, which allowed an analysis of complex mixtures of large glycans and determined the mass of the moiety to be 736.5 Da. Subsequently, multistage tandem MS and high-resolution measurements elucidated the structure. This success story illustrates the role of MS and the types of mass spectrometers potentially resolving a puzzling enigma in biology.