Global comparisons of lectin-glycan interactions using a database of analyzed glycan array data

Abstract

Lectin-glycan interactions have critical functions in multiple normal and pathological processes, but the binding partners and functions for many glycans and lectins are not known. An important step in better understanding glycan-lectin biology is enabling systematic quantification and analysis of the interactions. Glycan arrays can provide the experimental information for such analyses, and the thousands of glycan array datasets available through the Consortium for Functional Glycomics provide the opportunity to extend the analyses to a broad scale. We developed software, based on our previously described Motif Segregation algorithm, for the automated analysis of glycan array data, and we analyzed the entire storehouse of 2883 datasets from the Consortium for Functional Glycomics. We mined the resulting database to make comparisons of specificities across multiple lectins and comparisons between glycans in their lectin receptors. Of the lectins in the database, viral lectins were the most different from other organism types, with specificities nearly always restricted to sialic acids, and mammalian lectins had the most diverse range of specificities. Certain mammalian lectins were unique in their specificities for sulfated glycans. Simple modifications to a lactosamine core structure radically altered the types of lectins that were highly specific for the glycan. Unmodified lactosamine was specifically recognized by plant, fungal, viral, and mammalian lectins; sialylation shifted the binding mainly to viral lectins; and sulfation resulted in mainly mammalian lectins with the highest specificities. We anticipate that this analysis program and database will be valuable in fundamental glycobiology studies, detailed analyses of lectin specificities, and practical applications in translational research.

Fig. 1.

The development of the database of lectin-motif interactions. Quantified glycan array data (A) are processed using the GlycoSearch software and the motif segregation algorithm to produce motif scores for each experiment (B). The analysis of a glycan array experiment of the lectin concanavalin A (ConA) is given as an example, in which the top-scoring motifs contain mannose, followed by motifs with terminal glucose (C). All glycan array datasets were downloaded from the CFG website, processed, and assembled into a database (D). A variety of query types can be applied to the database.

Fig. 2.

The top 30 motif scores. The motif score is indicated along the y-axis, the labels on the x-axis give the lectin name, and the color gives the organism category of each lectin. The motif type is indicated by the yellow squares below the lectin names. Only four motif types, all simple monosaccharides, are represented in the top 30.

Fig. 3.

Differences in lectin specificities between organism categories. A, for each motif, the motif scores were averaged across all lectins within each category. Motifs with an average score below 0.88 in all organism categories were removed for clarity, and the remaining data were clustered. The categories are indicated by the column labels, and the motifs by the row labels. B, the average motif scores within each category were normalized to a maximum value of 10 (the average motif scores within a category all were divided by the maximum average in that category and multiplied by 10) to show the relative motif ranks within each category. C, for each motif, the maximum individual motif score was extracted from each category. For example, for the motif “Terminal Galβ1,4-” the program found the best score among all fungal lectins, then among all viral lectins, etc. Motifs with no scores above 7.4 in any category were removed for clarity.

Fig. 4.

Differences between lactosamine classes in lectin recognition. For each motif defining a modification of lactosamine, the lectins with the top 20 motif scores for that motif were extracted from the database. Replicate experiments of the same lectin were removed. Within each list of 20 lectins, the number of representatives from each organism type was tallied, as indicated in panel A. The range of motif scores is indicated for each group of lectins in panel B.