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DC Field | Value | Language |
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dc.contributor.author | Erausquin, E. | - |
dc.contributor.author | Serra, P. | - |
dc.contributor.author | Parras, D. | - |
dc.contributor.author | Santamaria, P. | - |
dc.contributor.author | López Sagaseta, J. | - |
dc.date.accessioned | 2024-01-30T14:44:05Z | - |
dc.date.available | 2024-01-30T14:44:05Z | - |
dc.date.issued | 2022-07-28 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | http://hdl.handle.net/2445/206648 | - |
dc.description.abstract | We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-Ag7-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-Ag7 complex, both in isolation as well as bound to the 4.1-TCR. We find that HIP promiscuity of the 4.1-TCR is dictated, on the one hand, by an amino acid sequence pattern that ensures I-Ag7 binding and, on the other hand, by the presence of three acidic residues at positions P5, P7 and P8 that favor an optimal engagement by the 4.1-TCR's complementary determining regions. Surprisingly, comparison of the TCR-bound and unbound HIP/I-Ag7 structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-Ag7 molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-Ag7 molecule is structurally malleable and that this plasticity allows the recognition of multiple peptides by individual TCRs that would otherwise be unable to do so.Copyright © 2022 Erausquin, Serra, Parras, Santamaria and López-Sagaseta. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media S.A. | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.924311 | - |
dc.relation.ispartof | Frontiers In Immunology, 2022, vol. 13, p. 924311 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2022.924311 | - |
dc.rights | cc by (c) Erausquin, E. et al., 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) | - |
dc.subject.classification | Seqüència d'aminoàcids | - |
dc.subject.classification | Insulina | - |
dc.subject.other | Amino acid sequence | - |
dc.subject.other | Insulin | - |
dc.title | Structural plasticity in I-Ag7 links autoreactivity to hybrid insulin peptides in type I diabetes | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2023-06-28T08:21:10Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.idimarina | 9328929 | - |
dc.identifier.pmid | 35967292 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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File | Description | Size | Format | |
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Structural plasticity in I-Ag7 links autoreactivity_FrontiersInImmunology.pdf | 17.22 MB | Adobe PDF | View/Open |
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