Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2012

Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation.

Abstract

During B cell differentiation in the bone marrow, the expression and activation of the pre-B cell receptor (pre-BCR) constitute crucial checkpoints for B cell development. Both constitutive and ligand-dependent pre-BCR activation modes have been described. The pre-BCR constitutes an immunoglobulin heavy chain (Ig?) and a surrogate light chain composed of the invariant ?5 and VpreB proteins. We previously showed that galectin-1 (GAL1), produced by bone marrow stromal cells, is a pre-BCR ligand that induces receptor clustering, leading to efficient pre-BII cell proliferation and differentiation. GAL1 interacts with the pre-BCR via the unique region of ?5 (?5-UR). Here, we investigated the solution structure of a minimal ?5-UR motif that interacts with GAL1. This motif adopts a stable helical conformation that docks onto a GAL1 hydrophobic surface adjacent to its carbohydrate binding site. We identified key hydrophobic residues from the ?5-UR as crucial for the interaction with GAL1 and for pre-BCR clustering. These residues involved in GAL1-induced pre-BCR activation are different from those essential for autonomous receptor activation. Overall, our results indicate that constitutive and ligand-induced pre-BCR activation could occur in a complementary manner.
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hal-01458259 , version 1 (27-05-2021)

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Latifa El Antak, Marion Espeli, Annie Boned, Olivier Bornet, Jeremy Bonzi, et al.. Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation.. Journal of Biological Chemistry, 2012, 287 (53), pp.44703--13. ⟨10.1074/jbc.M112.395152⟩. ⟨hal-01458259⟩
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