Lanig H, Bradl H, Jäck HM (2004)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2004
Book Volume: 40
Pages Range: 1263-72
Journal Issue: 17
DOI: 10.1016/j.molimm.2003.11.030
Signals delivered by the immunoglobulin (Ig)-like pre-B-cell receptor (pre-BCR) are critical for efficient maturation of early precursor B (pre-B) cells. A pre-BCR contains two immunoglobulin mu-heavy chains (muHC), two surrogate light chains (SLC) consisting of the non-covalently associated polypeptides, VpreB and lambda5, and the heterodimeric signaling transducer Igalpha/beta. Although, it is generally accepted that signals initiated from the pre-BCR are required for efficient expansion and differentiation of pre-B cells, the three-dimensional structure of this receptor has not yet been determined by either NMR or X-ray spectroscopy. Therefore, we used indirect computer-assisted molecular modeling techniques to predict for the first time three-dimensional coordinates of the pre-BCR, the conformation of the SLC components, VpreB and lambda5, and the position and flexibility of the so-called non-Ig-like unique tails at the C-terminus of VpreB and the N-terminus of lambda5. Structure prediction revealed that these unique tails of VpreB and lambda5 protrude from the SLC at the position where the CDR3 of a conventional IgLchain would be located. Thus, the unique tails are accessible for ligand binding, which supports the recent finding that the lambda5 unique tail is required for pre-BCR/stroma cell interaction. Further, the non-covalent interaction of the extra beta-strand of lambda5 (beta8) with VpreB is predicted to result in a stabilization of the tertiary structure of VpreB. In summary, three-dimensional computer modeling suggests that the structure of a pre-BCR resembles that of a conventional B-cell receptor (BCR) and that the lambda5 unique tail could be a major binding site for pre-BCR ligands.
APA:
Lanig, H., Bradl, H., & Jäck, H.-M. (2004). Three-dimensional modeling of a pre-B-cell receptor. Molecular Immunology, 40(17), 1263-72. https://doi.org/10.1016/j.molimm.2003.11.030
MLA:
Lanig, Harald, Harald Bradl, and Hans-Martin Jäck. "Three-dimensional modeling of a pre-B-cell receptor." Molecular Immunology 40.17 (2004): 1263-72.
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