Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations
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 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02947/full |
| _version_ | 1818507134902468608 |
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| author | Mario D. Friess Kristyna Pluhackova Rainer A. Böckmann |
| author_facet | Mario D. Friess Kristyna Pluhackova Rainer A. Böckmann |
| author_sort | Mario D. Friess |
| collection | DOAJ |
| description | 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-α/Ig-β heterodimer. The mIgM homodimer is based on an asymmetric association of two mIgM domains. We show that a specific site of the Ig-α/Ig-β 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. |
| first_indexed | 2024-12-10T22:14:26Z |
| format | Article |
| id | doaj.art-13c2baee772342ae9f9acc99fbd60aea |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T22:14:26Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-13c2baee772342ae9f9acc99fbd60aea2022-12-22T01:31:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02947423375Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics SimulationsMario D. FriessKristyna PluhackovaRainer A. BöckmannAntigen 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-α/Ig-β heterodimer. The mIgM homodimer is based on an asymmetric association of two mIgM domains. We show that a specific site of the Ig-α/Ig-β 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02947/fullB-cell receptortransmembrane domainnanodomainsself-assemblymolecular dynamics simulationscoarse-grained simulations |
| spellingShingle | Mario D. Friess Kristyna Pluhackova Rainer A. Böckmann Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations Frontiers in Immunology B-cell receptor transmembrane domain nanodomains self-assembly molecular dynamics simulations coarse-grained simulations |
| title | Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations |
| title_full | Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations |
| title_fullStr | Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations |
| title_full_unstemmed | Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations |
| title_short | Structural Model of the mIgM B-Cell Receptor Transmembrane Domain From Self-Association Molecular Dynamics Simulations |
| title_sort | structural model of the migm b cell receptor transmembrane domain from self association molecular dynamics simulations |
| topic | B-cell receptor transmembrane domain nanodomains self-assembly molecular dynamics simulations coarse-grained simulations |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02947/full |
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