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Data for Characterization of interactions within the Igα/Igβ transmembrane domains of the human B-cell receptor provides insights into receptor assembly
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Lockey, Christine, Young, Hannah, Brown, Jessica and Dixon, Ann M. (2022) Data for Characterization of interactions within the Igα/Igβ transmembrane domains of the human B-cell receptor provides insights into receptor assembly. [Dataset]
![[img]](https://wrap.warwick.ac.uk/style/images/fileicons/application_vnd.ms-excel.png) |
Microsoft Excel (GALLEX, CD and fluorescence data )
Lockey et al metadata.xlsx - Published Version Available under License Creative Commons Attribution 4.0. Download (232Kb) |
Official URL: http://wrap.warwick.ac.uk/164368/
Abstract
The B-cell receptor (BCR), a complex comprised of a membrane-associated immunoglobulin (mIg) and the Igα/β heterodimer, is one of the most important immune receptors in humans and controls B-cell development, activity, selection, and death. BCR signaling plays key roles in autoimmune diseases and lymphoproliferative disorders yet, despite the clinical significance of this protein complex, key regions (i.e. the transmembrane domains) have yet to be structurally characterized. The mechanism for BCR signaling also remains unclear, and has been variously described by the mutually exclusive crosslinking and dissociation activation models. Common to these models is the significance of local plasma membrane composition, which implies that interactions between BCR transmembrane domains (TMDs) play a role in receptor functionality. Here we used an in vivo assay of TMD oligomerization called GALLEX alongside spectroscopic and computational methods to characterize the structures and interactions of human Igα and Igβ TMDs in detergent micelles and natural membranes. We observed weak self-association of the Igβ TMD and strong self-association of the Igα TMD, which scanning mutagenesis revealed was entirely stabilized by an E-X10-P motif. We also demonstrated strong heterotypic interactions between the Igα and Igβ TMDs both in vitro and in vivo, which scanning mutagenesis and computational models suggest is multiconfigurational but can accommodate distinct interaction sites for self- and heterotypic interactions of the Igα TMD. Taken together, these results demonstrate that the TMDs of the human B-cell receptor are sites of strong protein-protein interactions that may direct BCR assembly, ER retention, and immune signaling.
| Item Type: | Dataset | ||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology Q Science > QR Microbiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
| Type of Data: | Spectroscopic | ||||||||
| Library of Congress Subject Headings (LCSH): | B cells -- Receptors, Circular dichroism, Membrane proteins -- Metabolism, Protein-protein interactions, Lipids , Proteins -- Crosslinking | ||||||||
| Publisher: | University of Warwick, Department of Chemistry | ||||||||
| Official Date: | 6 April 2022 | ||||||||
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| Status: | Not Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Media of Output (format): | .xlsx | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Copyright Holders: | University of Warwick | ||||||||
| Description: | This file contains data from a genetic assay called GALLEX, as well as circular dichroism and fluorescence data. |
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| Date of first compliant deposit: | 6 April 2022 | ||||||||
| Date of first compliant Open Access: | 6 April 2022 | ||||||||
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