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Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing
Studies have suggested that MHC class I (MHC I) molecules fluctuate rapidly between numerous conformational states and these motions support peptide sampling. To date, MHC I intermediates are largely uncharacterized experimentally and remain elusive. Here, we present x-ray crystal structures of HLA-...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439229/ https://www.ncbi.nlm.nih.gov/pubmed/37596268 http://dx.doi.org/10.1038/s41467-023-40736-6 |
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author | Li, Lenong Peng, Xubiao Batliwala, Mansoor Bouvier, Marlene |
author_facet | Li, Lenong Peng, Xubiao Batliwala, Mansoor Bouvier, Marlene |
author_sort | Li, Lenong |
collection | PubMed |
description | Studies have suggested that MHC class I (MHC I) molecules fluctuate rapidly between numerous conformational states and these motions support peptide sampling. To date, MHC I intermediates are largely uncharacterized experimentally and remain elusive. Here, we present x-ray crystal structures of HLA-B8 loaded with 20mer peptides that show pronounced distortions at the N-terminus of the groove. Long stretches of N-terminal amino acid residues are missing in the electron density maps creating an open-ended groove. Our structures also reveal highly unusual features in MHC I-peptide interaction at the N-terminus of the groove. Molecular dynamics simulations indicate that the complexes have varying degrees of conformational flexibility in a manner consistent with the structures. We suggest that our structures have captured the remarkable molecular dynamics of MHC I-peptide interaction. The visualization of peptide-dependent conformational motions in MHC I is a major step forward in our conceptual understanding of dynamics in high-affinity peptide selection. |
format | Online Article Text |
id | pubmed-10439229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104392292023-08-20 Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing Li, Lenong Peng, Xubiao Batliwala, Mansoor Bouvier, Marlene Nat Commun Article Studies have suggested that MHC class I (MHC I) molecules fluctuate rapidly between numerous conformational states and these motions support peptide sampling. To date, MHC I intermediates are largely uncharacterized experimentally and remain elusive. Here, we present x-ray crystal structures of HLA-B8 loaded with 20mer peptides that show pronounced distortions at the N-terminus of the groove. Long stretches of N-terminal amino acid residues are missing in the electron density maps creating an open-ended groove. Our structures also reveal highly unusual features in MHC I-peptide interaction at the N-terminus of the groove. Molecular dynamics simulations indicate that the complexes have varying degrees of conformational flexibility in a manner consistent with the structures. We suggest that our structures have captured the remarkable molecular dynamics of MHC I-peptide interaction. The visualization of peptide-dependent conformational motions in MHC I is a major step forward in our conceptual understanding of dynamics in high-affinity peptide selection. Nature Publishing Group UK 2023-08-18 /pmc/articles/PMC10439229/ /pubmed/37596268 http://dx.doi.org/10.1038/s41467-023-40736-6 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li, Lenong Peng, Xubiao Batliwala, Mansoor Bouvier, Marlene Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title | Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title_full | Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title_fullStr | Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title_full_unstemmed | Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title_short | Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing |
title_sort | crystal structures of mhc class i complexes reveal the elusive intermediate conformations explored during peptide editing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439229/ https://www.ncbi.nlm.nih.gov/pubmed/37596268 http://dx.doi.org/10.1038/s41467-023-40736-6 |
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