Engineering galactose-binding activity into a C-type mannose-binding protein (original) (raw)

Nature volume 360, pages 183–186 (1992)Cite this article

Abstract

CALCIUM-DEPENDENT or C-type carbohydrate-recognition domains are homologous protein modules found in a variety of animal lectins1. Selective binding of sugars by these domains is essential for glycoprotein clearance, cell–cell adhesion and pathogen neutralization. Although various C-type carbohydrate-recognition domains share sequence identity ranging from 20 to 55%, their sugar-binding characteristics vary widely. The structure of a mannose-binding carbohydrate-recognition domain in complex with a saccharide ligand suggests that two glutamic acid–asparagine pairs are essential determinants of ligand binding by this domain2. In C-type lectins that bind galactose with higher affinity than mannose, one of these pairs is replaced by glutamine–aspartic acid. Here we shift the sequence of the mannose-binding protein to correspond to that found in galactose-binding domains in order to test the importance of these residues in sugar-binding selectivity. This simple switch in the position of a single amide group alters the binding activity of the domain so that galactose becomes the preferred ligand.

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  1. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, 10032, USA
    Kurt Drickamer

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  1. Kurt Drickamer
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Drickamer, K. Engineering galactose-binding activity into a C-type mannose-binding protein.Nature 360, 183–186 (1992). https://doi.org/10.1038/360183a0

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