A symmetric geometry of transmembrane domains inside the B cell antigen receptor complex

Gottwick, Cornelia; He, Xiaocui; Hofmann, Andreas; Vesper, Niklas; Reth, Michael ✉; Yang, Jianying ✉

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
  • Szociológiai Tudományos Bizottság: A
  • Gazdaságtudományi Doktori Minősítő Bizottság: C
  • SJR Scopus - Multidisciplinary: D1
Azonosítók
Szakterületek:
    B lymphocytes have the ability to sense thousands of structurally different antigens and produce cognate antibodies against these molecules. For this they carry on their surface multiple copies of the B cell antigen receptor (BCR) comprising the membrane-bound Ig (mIg) molecule and the Ig alpha/Ig beta heterodimer functioning as antigen binding and signal transducing components, respectively. The mIg is a symmetric complex of 2 identical membrane-bound heavy chains (mHC) and 2 identical light chains. How the symmetric mIg molecule is asymmetrically associated with only one Ig alpha/Ig beta heterodimer has been a puzzle. Here we describe that Ig alpha and Ig beta both carry on one side of their alpha-helical transmembrane domain a conserved amino acid motif. By a mutational analysis in combination with a BCR rebuilding approach, we show that this motif is required for the retention of unassembled Ig alpha or Ig beta molecules inside the endoplasmic reticulum and the binding of the Ig alpha/Ig beta heterodimer to the mIg molecule. We suggest that the BCR forms within the lipid bilayer of the membrane a symmetric Ig alpha-mHC: mHC-Ig beta complex that is stabilized by an aromatic proline-tyrosine interaction. Outside the membrane this symmetry is broken by the disulfide-bridged dimerization of the extracellular Ig domains of Ig alpha and Ig beta. However, symmetry of the receptor can be regained by a dimerization of 2 BCR complexes as suggested by the dissociation activation model.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2020-09-30 01:51