Hsp27 is an ATP-independent heat shock protein chaperone with myriad client protein interactors. Any one of several mutations of this protein causes Charcot-Marie-Tooth (CMT) disease, a heritable neuromuscular disorder. These mutations are located in the protein’s IXI regulatory domain and cause a disruption of chaperone-client interactions, resulting in a marked decrease in chaperone activity. Our lab has previously shown that the O-GlcNAc modification of wild-type Hsp27 in the IXI domain region significantly enhances the protein’s chaperone activity. We hypothesize that O-GlcNAcylation will rescue the anti-chaperone phenotypes imparted by five CMT mutations (T180I, P182L, P182S, S187L, and R188W). To this end, we are synthesizing five protein species bearing both the mutation of interest and a pre-O-GlcNAcylated threonine residue at T184 using solid phase peptide synthesis and expressed protein ligation. With these proteins in hand, we will test each in relation to recombinantly-expressed, non-glycosylated mutants <i>in vivo</i> to determine the ability of the modification to rescue these mutations.

Investigating O-GlcNAcylation of Hsp27 and its role in hereditary neuropathies

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.