Regulating cell surface glycosylation with a small-molecule switch.
Correct localization of Golgi-resident enzymes is essential for the formation of specific glycan epitopes. In this chapter, we describe a method to control the localization, and thus the activity, of an individual glycosyltransferase by administration of a small molecule. Our method takes advantage of the modularity of most Golgi-resident enzymes, which are composed of localization and catalytic domains. These domains can be physically separated and fused to the small molecule binding proteins FRB and FKBP, which dimerize in the presence of rapamycin. In this way, rapamycin serves as a "switch" for enzyme activity.
Dube
Danielle H
DH
Department of Chemistry, Stanford University, CA, USA.
de Graffenried
Christopher L
CL
Kohler
Jennifer J
JJ
D020134:Catalytic Domain; D000939:Epitopes; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000201:enzymology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020123:Sirolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000378:metabolism
D000939:Epitopes; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D011134:Polysaccharides; D016695:Glycosyltransferases; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus