Structural highlights
Disease
IGLL1_HUMAN Defects in IGLL1 are the cause of agammaglobulinemia type 2 (AGM2) [MIM:613500. It is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
Function
IGLL1_HUMAN Critical for B-cell development.[1]
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.
References
- ↑ Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME. Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. J Exp Med. 1998 Jan 5;187(1):71-7. PMID:9419212
- ↑ Elantak L, Espeli M, Boned A, Bornet O, Bonzi J, Gauthier L, Feracci M, Roche P, Guerlesquin F, Schiff C. Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation. J Biol Chem. 2012 Nov 2. PMID:23124203 doi:http://dx.doi.org/10.1074/jbc.M112.395152
