3 years ago

Quantitative Effects of O-Linked Glycans on Protein Folding

Quantitative Effects of O-Linked Glycans on Protein Folding
Xiaoyang Guan, Yuan Ruan, Theo N. Koelsch, Suzannah G. Miller, Yaohao Li, Xinfeng Wang, Amy H. Tran, Zhongping Tan, Lomax F. Pass, Patrick K. Chaffey
Protein O-glycosylation is a diverse, common, and important post-translational modification of both proteins inside the cell and those that are secreted or membrane-bound. Much work has shown that O-glycosylation can alter the structure, function, and physical properties of the proteins to which it is attached. One gap remaining in our understanding of O-glycoproteins is how O-glycans might affect the folding of proteins. Here, we took advantage of synthetic, homogeneous O-glycopeptides to show that certain glycosylation patterns have an intrinsic effect, independent of any cellular folding machinery, on the folding pathway of a model O-glycoprotein, a carbohydrate binding module (CBM) derived from the Trichoderma reesei cellulase TrCel7A. The strongest effect, a 6-fold increase in overall folding rate, was observed when a single O-mannose was the glycan, and the glycosylation site was near the N-terminus of the peptide sequence. We were also able to show that glycosylation patterns affected the kinetics of each step in unique ways, which may help to explain the observations made here. This work is a first step toward quantitative understanding of how O-glycosylation might control, through intrinsic means, the folding of O-glycoproteins. Such an understanding is expected to facilitate future investigations into the effects of glycosylation on more biological processes related to protein folding.

Publisher URL: http://dx.doi.org/10.1021/acs.biochem.7b00483

DOI: 10.1021/acs.biochem.7b00483

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