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


ABSTRACT: 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?/Ig? 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?/Ig? heterodimer has been a puzzle. Here we describe that Ig? and Ig? both carry on one side of their ?-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? or Ig? molecules inside the endoplasmic reticulum and the binding of the Ig?/Ig? heterodimer to the mIg molecule. We suggest that the BCR forms within the lipid bilayer of the membrane a symmetric Ig?-mHC:mHC-Ig? 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? and Ig?. However, symmetry of the receptor can be regained by a dimerization of 2 BCR complexes as suggested by the dissociation activation model.

SUBMITTER: Gottwick C 

PROVIDER: S-EPMC6613136 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Gottwick Cornelia C   He Xiaocui X   Hofmann Andreas A   Vesper Niklas N   Reth Michael M   Yang Jianying J  

Proceedings of the National Academy of Sciences of the United States of America 20190617 27


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 Igα/Igβ 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  ...[more]

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