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Discovering immunoreceptor coupling and organization motifs

The recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowi...

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Autor principal: Reth, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507400/
https://www.ncbi.nlm.nih.gov/pubmed/37731510
http://dx.doi.org/10.3389/fimmu.2023.1253412
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author Reth, Michael
author_facet Reth, Michael
author_sort Reth, Michael
collection PubMed
description The recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowing the molecular basis of antigen sensing by these receptors, a rational design of optimal vaccines is not possible. The existence of conserved amino acids (AAs) that are not involved in the subunit interaction suggests that antigen receptors form higher complexes and/or have lateral interactors that control their activity. Here, I describe evolutionary conserved leucine zipper (LZ) motifs within the transmembrane domains (TMD) of antigen and coreceptor components that are likely to be involved in the oligomerization and lateral interaction of antigen receptor complexes on T and B cells. These immunoreceptor coupling and organization motifs (ICOMs) are also found within the TMDs of other important receptor types and viral envelope proteins. This discovery suggests that antigen receptors do not function as isolated entities but rather as part of an ICOM-based interactome that controls their nanoscale organization on resting cells and their dynamic remodeling on activated lymphocytes.
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spelling pubmed-105074002023-09-20 Discovering immunoreceptor coupling and organization motifs Reth, Michael Front Immunol Immunology The recently determined cryo-EM structures of the T cell antigen receptor (TCR) and B cell antigen receptor (BCR) show in molecular details the interactions of the ligand-binding part with the signaling subunits but they do not reveal the signaling mechanism of these antigen receptors. Without knowing the molecular basis of antigen sensing by these receptors, a rational design of optimal vaccines is not possible. The existence of conserved amino acids (AAs) that are not involved in the subunit interaction suggests that antigen receptors form higher complexes and/or have lateral interactors that control their activity. Here, I describe evolutionary conserved leucine zipper (LZ) motifs within the transmembrane domains (TMD) of antigen and coreceptor components that are likely to be involved in the oligomerization and lateral interaction of antigen receptor complexes on T and B cells. These immunoreceptor coupling and organization motifs (ICOMs) are also found within the TMDs of other important receptor types and viral envelope proteins. This discovery suggests that antigen receptors do not function as isolated entities but rather as part of an ICOM-based interactome that controls their nanoscale organization on resting cells and their dynamic remodeling on activated lymphocytes. Frontiers Media S.A. 2023-09-04 /pmc/articles/PMC10507400/ /pubmed/37731510 http://dx.doi.org/10.3389/fimmu.2023.1253412 Text en Copyright © 2023 Reth https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Reth, Michael
Discovering immunoreceptor coupling and organization motifs
title Discovering immunoreceptor coupling and organization motifs
title_full Discovering immunoreceptor coupling and organization motifs
title_fullStr Discovering immunoreceptor coupling and organization motifs
title_full_unstemmed Discovering immunoreceptor coupling and organization motifs
title_short Discovering immunoreceptor coupling and organization motifs
title_sort discovering immunoreceptor coupling and organization motifs
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10507400/
https://www.ncbi.nlm.nih.gov/pubmed/37731510
http://dx.doi.org/10.3389/fimmu.2023.1253412
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