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Publication Abstract from PubMed

During B cell differentiation in the bone marrow, the expression and activation of the pre-B cell receptor (pre-BCR) constitutes a crucial checkpoint for B cell development. Both constitutive and ligand-dependent pre-BCR activation modes have been described. The pre-BCR is constituted of an immunoglobulin heavy chain (Igmu) and of a surrogate light chain (SLC) composed of the invariant lambda5 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 lambda5 (lambda5-UR). Here we investigated the solution structure of a minimal lambda5-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 (CBS). We identified key hydrophobic residues from the lambda5-UR as crucial for the interaction with GAL1 and for pre-BCR clustering. These residues involved in GAL1-induced pre-BCR activation are different to those essential for autonomous receptor activation. Overall, our results indicate that constitutive and ligand-induced pre-BCR activation could occur in a complementary manner.

Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation.,Elantak L, Espeli M, Boned A, Bornet O, Bonzi J, Gauthier L, Feracci M, Roche P, Guerlesquin F, Schiff C J Biol Chem. 2012 Nov 2. PMID:23124203^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.