Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations

Journal article
(Original article)


Publication Details

Author(s): Frieß M, Pluhackova K, Böckmann R
Journal: Frontiers in Immunology
Publisher: FRONTIERS MEDIA SA
Publication year: 2018
Volume: 9
ISSN: 1664-3224
Language: English


Abstract

Antigen binding to B-cell antigen receptors (BCRs) followed by signaling initiates the humoral immune response. The signaling is intimately coupled to nanoclustering of BCRs and their sorting to specific membrane domains, a process that is ruled by interactions between the BCR transmembrane domain and lipids. While the structure of the extracellular domains of BCRs has been resolved, little is known about the configuration of the constituting four immunoglobulin domains spanning the membrane. Here, we modeled the structure of the transmembrane (TM) domain of the IgM B-cell receptor using self-assembly coarse-grained molecular dynamics simulations. The obtained quaternary structure was validated against available experimental data and atomistic simulations. The IgM-BCR-TM domain configuration shows a 1:1 stoichiometry between the homodimeric membrane-bound domain of IgM (mIgM) and a Ig-alpha/Ig-beta heterodimer. The mIgM homodimer is based on an asymmetric association of two mIgM domains. We show that a specific site of the Ig-alpha/Ig-beta heterodimer is responsible for the association of IgM-BCRs with lipid rafts. Our results further suggest that this site is blocked in small-sized IgM-BCR clusters. The BCR TM structure provides a molecular basis for the previously suggested dissociation activation model of B-cell receptors. Self-assembly molecular dynamics simulations at the coarse-grained scale here proved as a versatile tool in the study of receptor complexes.


FAU Authors / FAU Editors

Böckmann, Rainer Prof. Dr.
Professur für Computational Biology
Frieß, Mario
Professur für Computational Biology
Pluhackova, Kristyna
Professur für Computational Biology


How to cite

APA:
Frieß, M., Pluhackova, K., & Böckmann, R. (2018). Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations. Frontiers in Immunology, 9. https://dx.doi.org/10.3389/fimmu.2018.02947

MLA:
Frieß, Mario, Kristyna Pluhackova, and Rainer Böckmann. "Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations." Frontiers in Immunology 9 (2018).

BibTeX: 

Last updated on 2019-17-04 at 08:18