The How and Why of Ca2+ Involvement in Lectin Activity

Abstract

Cell surface glycans are biochemical signals for communication with the environment. They are translated into biological responses by first binding to lectins, this recognition process thereupon triggering ensuing post-binding signaling. The specificity of this interaction must necessarily be exquisite to preclude errors. Toward this end Ca 2+ is recruited to the realm of protein-carbohydrate interactions. Intriguingly, not one but different strategies how Ca 2+ assists in singling out the correct sugar ligands are operative. This review dissects the different ways Ca 2+ functions as an integral component of various lectinsʼ carbohydrate-binding domains. It spans the range from the role of Ca 2+ in structurally organizing the contact site without direct interaction to the ligand to interplays with charged and even neutral ligands. Finally, a case of an intricate network of up to four coordination bonds of Ca 2+ with a galactose moiety is presented.

Lectins: Getting Familiar with Translators of the Sugar Code

“…Illustration of three examples of carbohydrate recognition domains (CRD) of mammalian lectins exemplifies the diversity of folds ( Figure 4 ). Notably, the C-type fold ( Figure 4 b) harbors a Ca 2+ in its center for topologically specific interplay with the ligand, a case of direct contact between the strategically positioned cation and the glycan, embedded in a network of hydrogen bonds between sugar and protein [ 41 , 46 ]. This orchestrated constellation, a sensor for complementarity, ensures monosaccharide specificity.…”

Glycoclusters as lectin inhibitors: comparative analysis on two plant agglutinins with different folding as a step towards rules for selectivity

“…When Ca 2+ was removed from the lectin by treatment with EDTA, abolishing the involvement of the cation in GalNAc binding by coordination bonds to the 3-and 4-OH groups, 8,23 no significant signal in the assay was obtained. The same holds true if the 4-OH group is in the equatorial position as is the case for the GlcNAc derivatives; these products are not suited for coordination bonding.…”

Pro4 prolyl peptide bond isomerization in human galectin-7 modulates the monomer-dimer equilibrum to affect function

“…In the case of lectins, the existence of two conformational states had first been reported with metal ion (Ca 2+ , Mn 2+ ) binding to concanavalin A [ 66 , 67 ]. Instead of being involved in coordination bonding with the glycan [ 68 ], these metal ions induce a series of conformational changes that eventually shaped the contact site for the sugar by allowing the side chain of N208 to ‘flop’ into its appropriate position [ 69 - 71 ]. At the heart of this process was trans - to cis- isomerization of a non-prolyl peptide bond at A207-N208 that promoted cation binding.…”