Protein O-GalNAcylation is an abundant post-translational modification and predicted to occur in over 80% of the proteins passing through the Golgi apparatus. This modification is driven by 20 polypeptide GaINAc (N-acetylgalactosamine)-transferases (GalNAc-Ts), which are unique in that they possess both catalytic and lectin domains. The peptide substrate specificities of GalNAc-Ts are still poorly defined and our understanding of the sequence and structural features that direct O-glycosylation of proteins is limited. Part of this may be attributed to the complex regulation by coordinated action of multiple GalNAc-T isoforms, and part of this may also be attributed to the two functional domains of GalNAc-Ts that both seems to be involved in directing the substrate specificities. Recent studies have resulted in 3D structures of GalNAc-Ts and determination of the reaction mechanism of this family of enzymes. Key advances include the trapping of binary/ternary complexes in combination with computational simulations and AFM/small-SAXS experiments, which have allowed for the dissection of the reaction coordinates and the mechanism by which the lectin domains modulate the glycosylation. These studies not only broaden our knowledge of the modes-of-action of this family of enzymes but also open up potential avenues for the rational design of effective and selective inhibitors of O-glycosylation.
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February 2016
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Scanning electron micrograph of a cell from the endosperm of a barley grain. The cell is tightly packed with large, disk-shaped (A-type) and much smaller, almost spherical (B-type) starch granules. The smooth areas in this image are the surface of the cell walls of neighbouring endosperm cells. For further details see pp. 157-163. Image kindly provided by Elaine Barclay and Vasilios Andriotis (John Innes Centre, Norwich). - PDF Icon PDF LinkTable of Contents
Review Article|
February 09 2016
Recent structural and mechanistic insights into protein O-GalNAc glycosylation
Ramon Hurtado-Guerrero
Ramon Hurtado-Guerrero
1
*Fundación ARAID, Edificio CEEI ARAGÓN, Zaragoza 50018, Spain
†Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, BIFI-IQFR (CSIC) Joint Unit, Mariano Esquillor s/n, Campus Rio Ebro, Edificio I+D, Zaragoza, Spain
1email rhurtado@bifi.es.
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Publisher: Portland Press Ltd
Received:
November 26 2015
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (1): 61–67.
Article history
Received:
November 26 2015
Citation
Ramon Hurtado-Guerrero; Recent structural and mechanistic insights into protein O-GalNAc glycosylation. Biochem Soc Trans 15 February 2016; 44 (1): 61–67. doi: https://doi.org/10.1042/BST20150178
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