8E4C

IgM BCR fab truncated form

8E4C の概要

• エントリーDOI: 10.2210/pdb8e4c/pdb
• EMDBエントリー: 27888
• 分子名称: Isoform 2 of Immunoglobulin heavy constant mu, B-cell antigen receptor complex-associated protein alpha chain,Yellow fluorescent protein, B-cell antigen receptor complex-associated protein beta chain, ... (4 entities in total)
• 機能のキーワード: complex, membrane protein, immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161203.22

構造登録者

Dong, Y.,Pi, X.,Wu, H.,Reth, M. (登録日: 2022-08-18, 公開日: 2022-11-16, 最終更新日: 2025-05-28)

主引用文献

Dong, Y.,Pi, X.,Bartels-Burgahn, F.,Saltukoglu, D.,Liang, Z.,Yang, J.,Alt, F.W.,Reth, M.,Wu, H.
Structural principles of B cell antigen receptor assembly.
Nature, 612:156-161, 2022

PubMed Abstract: The B cell antigen receptor (BCR) is composed of a membrane-bound class M, D, G, E or A immunoglobulin for antigen recognition and a disulfide-linked Igα (also known as CD79A) and Igβ (also known as CD79B) heterodimer (Igα/β) that functions as the signalling entity through intracellular immunoreceptor tyrosine-based activation motifs (ITAMs). 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 Igα/β heterodimer mainly uses Igα to associate with Cµ3 and Cµ4 domains of one heavy chain (µHC) while leaving the other heavy chain (µHC') unbound. The transmembrane domain (TMD) helices of µHC and µHC' interact with those of the Igα/β heterodimer to form a tight four-helix bundle. The asymmetry at the TMD prevents the recruitment of two Igα/β heterodimers. Notably, the connecting peptide between the ECD and TMD of µHC intervenes in between those of Igα and Igβ to guide TMD assembly through charge complementarity. Weaker but distinct density for the Igβ 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.

PubMed: 36228656
DOI: 10.1038/s41586-022-05412-7

実験手法

ELECTRON MICROSCOPY (4 Å)