Abstract
Galectins are glycan-binding proteins involved in various biological processes including cell/cell interactions. During B-cell development, bone marrow stromal cells secreting galectin-1 (GAL1) constitute a specific niche for pre-BII cells. Besides binding glycans, GAL1 is also a pre-B cell receptor (pre-BCR) ligand that induces receptor clustering, the first checkpoint of B-cell differentiation. The GAL1/pre-BCR interaction is the first example of a GAL1/unglycosylated protein interaction in the extracellular compartment. Here we show that GAL1/pre-BCR interaction modifies GAL1/glycan affinity and particularly inhibits binding to LacNAc containing epitopes. GAL1/pre-BCR interaction induces local conformational changes in the GAL1 carbohydrate-binding site generating a reduction in GAL1/glycan affinity. This fine tuning of GAL1/glycan interactions may be a strategic mechanism for allowing pre-BCR clustering and pre-BII cells departure from their niche. Altogether, our data suggest a novel mechanism for a cell to modify the equilibrium of the GAL1/glycan lattice involving GAL1/unglycosylated protein interactions.
Highlights
Galectins are glycan-binding proteins involved in various biological processes including cell/cell interactions
At the contact zone between pre-BII and stromal cells, GAL1, preBCRs and glycosylated integrins relocalize[18]. This relocalization is allowed by the dual interaction network of GAL1 with the pre-B cell receptor (pre-B-cell receptor (BCR)) and with glycosylated counter receptors at the cell surfaces[18,19,20]. This GAL1/pre-BCR interaction is the first example of a GAL1/unglycosylated protein interaction in the extracellular compartment
We recently found that GAL1 interacts with a l5-UR motif, l5-UR22-45, of the pre-BCR that adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to the CBS26
Summary
Galectins are glycan-binding proteins involved in various biological processes including cell/cell interactions. GAL1/pre-BCR interaction induces local conformational changes in the GAL1 carbohydrate-binding site generating a reduction in GAL1/glycan affinity. The multivalent nature of both lectins and their saccharide ligands allows the formation of a lectin–carbohydrate lattice, which acts as a signalling complex at the cell surface These lectin– glycoprotein lattices are characterized by multiple low-affinity interactions, resulting in high overall avidity[3,4,5]. On l5-UR binding, the lactose-binding activity of GAL1 undergoes a fourfold decrease, while no binding affinity changes have been observed for GAL1/ l5-UR22-45 interaction in the presence versus in the absence of lactose[26] These modulations suggest that the pre-BCR could modulate GAL1 affinity for specific glycoproteins[26] by a mechanism that would be a strategic step at the synapse level to modify the crosslinked lattices. There are many text book cases where a stronger or weaker binding activity of one protein is induced by another protein or smaller molecule, but the molecular and structural basis of such effects have not been described yet for the carbohydrate-binding activity of galectins
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