Protein O-glycosylation in plants
The protein O-glycosylation group focuses on O-linked glycosylation of proteins in plants and animal cells and on its translational potential within disease / allergy and production of compatible glycoprotein therapeutics. O-glycosylation in plants is a two-step process where prolines are converted to Hydroxyprolines within distinct amino acid motives by glycosylation defining enzymes (prolyl hydroxylases) and then O-glycosylated by sets of glycosylation defining enzymes (glycosyltransferases).
Our progress on the genetic regulation of glycosylation machineries in plant and mammalian cells may through the use of precise genetic engineering technologies enable production of proteins with compatible or immune stimulatory defined glycans. These defined glycans may for example be used to target specific receptors of the human innate immune system ultimately leading to tolerance or immunity with the prospects of developing allergy or cancer vaccines. More specifically, our recent identification of glycosylation enzymes that glycosylates plant cell wall glycoproteins, the extensin (EXT) and ArabinoGalactan Proteins (AGPs), has opened up for genetically engineered control of glycosylation- defining and -initiating enzymes in plants or microorganisms.
- Halim A, Larsen ISB, Neubert P, Joshi H., Petersen BL, Vakhrushev SY, Strahl,S, Clausen H (2015) Discovery of a Nucleocytoplasmic O-Mannose Glycoproteome in Yeast. Proc Natl Acad Sci US, in press
- Halim A, Carlsson MC, Madsen CB, Brand S, Møller SR, Olsen CE, Vakhrushev SY, Clausen H, Brimnes J, Wurtzen PA, Ipsen H, Petersen BL, Wandall H (2015) Top-down and bottom-up mass spectrometry of seven major allergenic proteins reveal novel post translational modifications. Mol Cell Proteomics 14:191-204
- Velasquez S.M., Martiniano MR, Mangano S, Juarez SPD, Marzol E, Möller SR, Salter JDS, Dorosz JAG, Borassi C, Po-Fachin L, Dilokpimol A, Dong W, Ligabue-Braun R, Buono R, Marcus S, Aptekman A, Halim A, Dinneny JR, Otegui M, Knox P, Nadra A, Verli H, Bauer S, Held M, Geshi N, Petersen BL, Iusem ND, Estevez JM (2014) Complex regulation of Prolyl-4-hydroxylases impacts root hair expansion. Mol Plant 8(5):734-46
- Yang Z, Drew DP, Jørgensen B, Levery SB, Bach SS, Ulvskov P, Bennett EP, Clausen H, Petersen BL (2012) Engineering mammalian mucin-type O-glycosylation in plants. J Biol Chem 287:11911-11923
- Velasquez SM, Ricardi MM, Dorosz JG, Fernandez PV, Nadra AD, Pol-Fachin L, Egelund J, Gille S, Ciancia M, Verli H, Pauly M, Bacic A, Olsen CE, Ulvskov P, Petersen BL, Somerville C, Iusem ND, Estevez JM (2011) Essential role of O-glycosylated cell wall proteins in polarized root hair growth. Science 332:1401-1403
US-Patent (US9024110): Yang Z, Bennett EP, Arigi EA, Drew DP, Levery SB, Ulvskov P, Clausen H, Petersen BL (2011) ’Method for engineering the initiation of mammalian O-glycosylation