Comprehensive analysis of lectin-glycan interactions reveals determinants of lectin specificity

by Daniel E. Mattox, Chris Bailey-Kellogg Lectin-glycan interactions facilitate inter- and intracellular communication in many processes including protein trafficking, host-pathogen recognition, and tumorigenesis promotion. Specific recognition of glycans by lectins is also the basis for a wide range of applications in areas including gly cobiology research, cancer screening, and antiviral therapeutics. To provide a better understanding of the determinants of lectin-glycan interaction specificity and support such applications, this study comprehensively investigates specificity-conferring features of all available lectin-glycan compl ex structures. Systematic characterization, comparison, and predictive modeling of a set of 221 complementary physicochemical and geometric features representing these interactions highlighted specificity-conferring features with potential mechanistic insight. Univariable comparative analyses with w eighted Wilcoxon-Mann-Whitney tests revealed strong statistical associations between binding site features and specificity that are conserved across unrelated lectin binding sites. Multivariable modeling with random forests demonstrated the utility of these features for predicting the identity of bo und glycans based on generalized patterns learned from non-homologous lectins. These analyses revealedglobal determinants of lectin specificity, such as sialic acid glycan recognition in deep, concave binding sites enriched for positively charged residues...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research