Molecule of the Month
May 2020
Structure and Mechanism of the ER-Based Glucosyltransferase ALG6

In eukarya proteinN-glycosylation, a series of reactions occurs within the endoplasmic reticulum (ER) where a dolichylpyrophosphate-linked oligosaccharide is assembled stepwise. We used synthetic analogues of dolichylphosphate-linked and dolichylpyrophosphate-linked sugars and purified enzymes of the ALG pathway to elongate the glycan and recapitulate the activity of ALG6 in vitro.
The structure of ALG6 was determined by cryo-EM in the apo state (3.0) and substrate bound (3.9). Our results define the architecture of ER-luminal GT-C enzymes and provide a structural basis for understanding their catalytic mechanisms.

This work was carried out in the group of Prof. Jean-Louis Reymond.


  • J. S. Bloch, G. Pesciullesi, J. Boilevin, K. Nosol, R. N. Irobalieva, T. Darbre, M. Aebi, A. A. Kossiakoff, J.-L. Reymond, K. P. Locher;
    "Structure and mechanism of the ER-based glucosyltransferase ALG6"
    Nature, 2020, 579(7799), 443-447; doi:10.1038/s41586-020-2044-z.