PDBsum entry 4z78

Immune system

PDB id: 4z78

Contents

Protein chains

277 a.a.

100 a.a.

Ligands

LEU-TYR-LEU-VAL-CYS-GLY-GLU-ARG-GLY-PHE ×3

EDO ×5

GOL ×6

SO4 ×9

Waters ×364

References listed in PDB file

Key reference

• Title: Distortion of the major histocompatibility complex class i binding groove to accommodate an insulin-Derived 10-Mer peptide.
• Authors: C.Motozono, J.A.Pearson, E.De leenheer, P.J.Rizkallah, K.Beck, A.Trimby, A.K.Sewell, F.S.Wong, D.K.Cole.
• Ref.: J Biol Chem, 2015, 290, 18924-18933. [DOI no: 10.1074/jbc.M114.622522]
• PubMed id: 26085090

Abstract

The non-obese diabetic mouse model of type 1 diabetes continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic β-cells. However, little is known about the molecular mechanisms that enable this disease pathway. We show that insulin reactivity by a CD8(+) T-cell clone, known to induce type 1 diabetes, is characterized by weak T-cell antigen receptor binding to a relatively unstable peptide-MHC. The structure of the native 9- and 10-mer insulin epitopes demonstrated that peptide residues 7 and 8 form a prominent solvent-exposed bulge that could potentially be the main focus of T-cell receptor binding. The C terminus of the peptide governed peptide-MHC stability. Unexpectedly, we further demonstrate a novel mode of flexible peptide presentation in which the MHC peptide-binding groove is able to "open the back door" to accommodate extra C-terminal peptide residues.