title: Photoactivatable glycopolymers for the proteome-wide identification of fucose-α(1-2)-galactose binding proteins.
abstract: Although fucose-α(1-2)-galactose (Fucα(1-2)Gal)-containing glycans have been implicated in cognitive processes such as learning and memory, their precise molecular mechanisms are poorly understood. Here we employed the use of multivalent glycopolymers to enable the first proteome-wide identification of weak affinity, low abundance Fucα(1-2)Gal glycan-binding proteins (GBPs). Biotin-terminated glycopolymers containing photoactivatable cross-linking groups were designed to capture and enrich GBPs from rat brain lysates. Candidate proteins were tested for their ability to bind Fucα(1-2)Gal, and the functional significance of the interaction was investigated for the synaptic vesicle protein SV2a using a knockout mouse system. The results suggest a role for SV2a-Fucα(1-2)Gal interactions in SV2a trafficking and synaptic vesicle recycling. More broadly, our studies outline a general chemical approach for the systems-level discovery of novel GBPs.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology and Howard Hughes Medical Institute , 1200 East California Boulevard, Pasadena, California 91125, United States.
authors.forename: Arif
authors.initials: A
authors.lastname: Wibowo
authors.forename: Eric C
authors.initials: EC
authors.lastname: Peters
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hsieh-Wilson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005690:Galactose / Q000031:analogs & derivatives / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D055668:Photochemical Processes; D011134:Polysaccharides / Q000378:metabolism* / Q000528:radiation effects*; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
chemical_list: D011134:Polysaccharides; D020543:Proteome; D005690:Galactose