7QHP
Structure of I-Ag7 with a bound hybrid insulin peptide
Summary for 7QHP
| Entry DOI | 10.2210/pdb7qhp/pdb |
| Descriptor | H-2 class II histocompatibility antigen, A-D alpha chain, Murine MHC class II I-A beta g7, Insulin-1, ... (7 entities in total) |
| Functional Keywords | diabetes, mhc class ii, hybrid insulin peptide, autoimmune disease, immune system |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 3 |
| Total formula weight | 51062.61 |
| Authors | Lopez-Sagaseta, J.,Erausquin, E. (deposition date: 2021-12-13, release date: 2022-07-20, Last modification date: 2024-10-23) |
| Primary citation | Erausquin, E.,Serra, P.,Parras, D.,Santamaria, P.,Lopez-Sagaseta, J. Structural plasticity in I-A g7 links autoreactivity to hybrid insulin peptides in type I diabetes. Front Immunol, 13:924311-924311, 2022 Cited by PubMed Abstract: We recently provided evidence for promiscuous recognition of several different hybrid insulin peptides (HIPs) by the highly diabetogenic, I-A-restricted 4.1-T cell receptor (TCR). To understand the structural determinants of this phenomenon, we solved the structure of an agonistic HIP/I-A 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-A 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-A structures reveals that 4.1-TCR binding triggers several novel and unique structural motions in both the I-A molecule and the peptide that are essential for docking. This observation indicates that the type 1 diabetes-associated I-A 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. PubMed: 35967292DOI: 10.3389/fimmu.2022.924311 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.82 Å) |
Structure validation
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