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Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing

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  • Lenong Li

    (University of Illinois)

  • Xubiao Peng

    (School of Physics, Beijing Institute of Technology)

  • Mansoor Batliwala

    (University of Illinois)

  • Marlene Bouvier

    (University of Illinois)

Abstract

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.

Suggested Citation

  • Lenong Li & Xubiao Peng & Mansoor Batliwala & Marlene Bouvier, 2023. "Crystal structures of MHC class I complexes reveal the elusive intermediate conformations explored during peptide editing," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40736-6
    DOI: 10.1038/s41467-023-40736-6
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    References listed on IDEAS

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    1. Alexander Domnick & Christian Winter & Lukas Sušac & Leon Hennecke & Mario Hensen & Nicole Zitzmann & Simon Trowitzsch & Christoph Thomas & Robert Tampé, 2022. "Molecular basis of MHC I quality control in the peptide loading complex," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Raghavendra Anjanappa & Maria Garcia-Alai & Janine-Denise Kopicki & Julia Lockhauserbäumer & Mohamed Aboelmagd & Janina Hinrichs & Ioana Maria Nemtanu & Charlotte Uetrecht & Martin Zacharias & Sebasti, 2020. "Structures of peptide-free and partially loaded MHC class I molecules reveal mechanisms of peptide selection," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Andreas Blees & Dovile Januliene & Tommy Hofmann & Nicole Koller & Carla Schmidt & Simon Trowitzsch & Arne Moeller & Robert Tampé, 2017. "Structure of the human MHC-I peptide-loading complex," Nature, Nature, vol. 551(7681), pages 525-528, November.
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