BIO

For many years I have been studying the mechanism by which oligosaccharides are added to proteins in the lumen of the endoplasmic reticulum and the effect that such bulky, highly hydrophilic structures have on the acquisition by glycoproteins of their proper tertiary structure. I described first that in mammalian cells an oligosaccharide is transferred "en bloc" from a lipid (dolichol) pyrophosphate derivative to asparagine units in proteins and obtained hints that this compound was further processed once transferred.  I conducted then further studies that revealed that the same glycosylation mechanism is operative in the common yeast Saccharomyces cerevisiae, in which it may lead to synthesis of mannan, a cell wall polysaccharide.  Studies on protein glycosylation conducted in my laboratory showed, first in trypanosomatid protozoa and then in mammalian cells, that protein-linked saccharides are transiently glucosylated in the endoplasmic reticulum.  The enzyme responsible for glucosylation (UDP-Glc:glcopprotein glucosyltransferase) appeared to behave as a sensor of glycoprotein conformations as it only glucosylates saccharides linked to improperly folded protein moieties.  The glucosyltransferase is a key element in the endoplasmic reticulum retention of malfolded conformers and in the mechanism by which glycoproteins acquire their native three-dimensional structures.

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