Three-dimensional modeling of a pre-B-cell receptor

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• 作者：Lanig ; Harald ; Bradl ; Harald ; Jä ; ck ; Hans-Martin
• 关键词：μ ; HC ; heavy chain of IgM ; SL ; surrogate light ; pre-BCR ; pre-B-cell receptor ; Fdμ ; truncated μ ; HC comprising a V_H and the first C_H domain of a μ ; HC ; B-cell maturation ; VpreB ; λ ; 5 ; Unique tails ; Molecular modeling
• 刊名：Molecular Immunology
• 出版年：2004
• 出版时间：March, 2004
• 年：2004
• 卷：40
• 期：17
• 页码：1263-1272
• 全文大小：331 K

文摘

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 μ-heavy chains (μHC), two surrogate light chains (SLC) consisting of the non-covalently associated polypeptides, VpreB and λ5, and the heterodimeric signaling transducer Igα/β. 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 λ5, 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 λ5. Structure prediction revealed that these unique tails of VpreB and λ5 protrude from the SLC at the position where the CDR3 of a conventional IgL chain would be located. Thus, the unique tails are accessible for ligand binding, which supports the recent finding that the λ5 unique tail is required for pre-BCR/stroma cell interaction. Further, the non-covalent interaction of the extra β-strand of λ5 (β8) 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 λ5 unique tail could be a major binding site for pre-BCR ligands.