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Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First

Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β(2)-microglobulin (β(2)-...

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Autores principales: Wu, Yanan, Zhang, Nianzhi, Hashimoto, Keiichiro, Xia, Chun, Dijkstra, Johannes M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236899/
https://www.ncbi.nlm.nih.gov/pubmed/34194421
http://dx.doi.org/10.3389/fimmu.2021.621153
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author Wu, Yanan
Zhang, Nianzhi
Hashimoto, Keiichiro
Xia, Chun
Dijkstra, Johannes M.
author_facet Wu, Yanan
Zhang, Nianzhi
Hashimoto, Keiichiro
Xia, Chun
Dijkstra, Johannes M.
author_sort Wu, Yanan
collection PubMed
description Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β(2)-microglobulin (β(2)-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species. In the present study, a comprehensive comparison of pMHC-I and pMHC-II structures helps to understand pMHC structural evolution and supports the earlier proposed—though debated—direction of MHC evolution from class II-type to class I. Extant pMHC-II structures share major functional characteristics with a deduced MHC-II-type homodimer ancestor. Evolutionary establishment of pMHC-I presumably involved important new functions such as (i) increased peptide selectivity by binding the peptides in a closed groove (ii), structural amplification of peptide ligand sequence differences by binding in a non-relaxed fashion, and (iii) increased peptide selectivity by syngeneic heterotrimer complex formation between peptide, HC, and β(2)-m. These new functions were associated with structures that since their establishment in early pMHC-I have been very well conserved, including a shifted and reorganized P1 pocket (aka A pocket), and insertion of a β(2)-m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of peptide binding domains among MHC-I than among MHC-II, agreeing with more demanding interactions within pMHC-I complexes. In lungfishes, genes encoding fusions of all MHC-IIα and MHC-IIβ extracellular domains were identified, and although these lungfish genes presumably derived from classical MHC-II, they provide an alternative mechanistic hypothesis for how evolution from class II-type to class I may have occurred.
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spelling pubmed-82368992021-06-29 Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First Wu, Yanan Zhang, Nianzhi Hashimoto, Keiichiro Xia, Chun Dijkstra, Johannes M. Front Immunol Immunology Structures of peptide-loaded major histocompatibility complex class I (pMHC-I) and class II (pMHC-II) complexes are similar. However, whereas pMHC-II complexes include similar-sized IIα and IIβ chains, pMHC-I complexes include a heavy chain (HC) and a single domain molecule β(2)-microglobulin (β(2)-m). Recently, we elucidated several pMHC-I and pMHC-II structures of primitive vertebrate species. In the present study, a comprehensive comparison of pMHC-I and pMHC-II structures helps to understand pMHC structural evolution and supports the earlier proposed—though debated—direction of MHC evolution from class II-type to class I. Extant pMHC-II structures share major functional characteristics with a deduced MHC-II-type homodimer ancestor. Evolutionary establishment of pMHC-I presumably involved important new functions such as (i) increased peptide selectivity by binding the peptides in a closed groove (ii), structural amplification of peptide ligand sequence differences by binding in a non-relaxed fashion, and (iii) increased peptide selectivity by syngeneic heterotrimer complex formation between peptide, HC, and β(2)-m. These new functions were associated with structures that since their establishment in early pMHC-I have been very well conserved, including a shifted and reorganized P1 pocket (aka A pocket), and insertion of a β(2)-m hydrophobic knob into the peptide binding domain β-sheet floor. A comparison between divergent species indicates better sequence conservation of peptide binding domains among MHC-I than among MHC-II, agreeing with more demanding interactions within pMHC-I complexes. In lungfishes, genes encoding fusions of all MHC-IIα and MHC-IIβ extracellular domains were identified, and although these lungfish genes presumably derived from classical MHC-II, they provide an alternative mechanistic hypothesis for how evolution from class II-type to class I may have occurred. Frontiers Media S.A. 2021-06-14 /pmc/articles/PMC8236899/ /pubmed/34194421 http://dx.doi.org/10.3389/fimmu.2021.621153 Text en Copyright © 2021 Wu, Zhang, Hashimoto, Xia and Dijkstra 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
Wu, Yanan
Zhang, Nianzhi
Hashimoto, Keiichiro
Xia, Chun
Dijkstra, Johannes M.
Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title_full Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title_fullStr Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title_full_unstemmed Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title_short Structural Comparison Between MHC Classes I and II; in Evolution, a Class-II-Like Molecule Probably Came First
title_sort structural comparison between mhc classes i and ii; in evolution, a class-ii-like molecule probably came first
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236899/
https://www.ncbi.nlm.nih.gov/pubmed/34194421
http://dx.doi.org/10.3389/fimmu.2021.621153
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