Laura Kiessling, PhD
Us Versus Them: Targeting Microbial Cell Surface Glycosylation
University of Wisconsin, Madison
Director, Keck Center for Chemical Genomics
Steenbock Professor of Chemistry
Laurens Anderson Professor of Biochemistry
1994 Beckman Young Investigator
Humans must fight off microbes that they encounter in the environment. Means of distinguishing between host and microbial guests must therefore exist, but the molecular mechanisms by which such distinctions are made have not been fully elucidated. The glycans displayed on mammalian cell surfaces can differ markedly from those on microbes. Carbohydrate-binding proteins (lectins) that selectively recognize microbial glycans could be useful detectors, but the human lectins described to date can bind human glycans. We used high throughput chemical tools to identify a human lectin that fails to bind known human glycan epitopes but rather interacts with multiple, distinct glycan epitopes found exclusively on microbes. To probe how this protein discriminates between human and microbial glycans, we determined X-ray crystallography to determine this lectin’s structure. This first member of a new structural class reveals the molecular basis for its paradoxical ability to bind many microbial glycans but yet avoid interaction with human glycans. The selectivity of this human protein suggests it functions in microbial surveillance and that its recognition properties might be harnessed to yield new strategies for diagnostic or delivery agents that exploit its selectively for microbial glycans.