8e4c

Publication Abstract from PubMed

The B cell antigen receptor (BCR) is composed of a membrane-bound class M, D, G, E or A immunoglobulin for antigen recognition(1-3) and a disulfide-linked Igalpha (also known as CD79A) and Igbeta (also known as CD79B) heterodimer (Igalpha/beta) that functions as the signalling entity through intracellular immunoreceptor tyrosine-based activation motifs (ITAMs)(4,5). The organizing principle of the BCR remains unknown. Here we report cryo-electron microscopy structures of mouse full-length IgM BCR and its Fab-deleted form. At the ectodomain (ECD), the Igalpha/beta heterodimer mainly uses Igalpha to associate with Cmicro3 and Cmicro4 domains of one heavy chain (microHC) while leaving the other heavy chain (microHC') unbound. The transmembrane domain (TMD) helices of microHC and microHC' interact with those of the Igalpha/beta heterodimer to form a tight four-helix bundle. The asymmetry at the TMD prevents the recruitment of two Igalpha/beta heterodimers. Notably, the connecting peptide between the ECD and TMD of microHC intervenes in between those of Igalpha and Igbeta to guide TMD assembly through charge complementarity. Weaker but distinct density for the Igbeta ITAM nestles next to the TMD, suggesting potential autoinhibition of ITAM phosphorylation. Interfacial analyses suggest that all BCR classes utilize a general organizational architecture. Our studies provide a structural platform for understanding B cell signalling and designing rational therapies against BCR-mediated diseases.

Structural principles of B cell antigen receptor assembly.,Dong Y, Pi X, Bartels-Burgahn F, Saltukoglu D, Liang Z, Yang J, Alt FW, Reth M, Wu H Nature. 2022 Dec;612(7938):156-161. doi: 10.1038/s41586-022-05412-7. Epub 2022 , Oct 13. PMID:36228656^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.