7P4B

HLA-E*01:03 in complex with IL9

Summary for 7P4B

• Entry DOI: 10.2210/pdb7p4b/pdb
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, ESAT-6-like protein EsxH, ... (8 entities in total)
• Functional Keywords: hla-e mhc, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 182347.10

Authors

Walters, L.C.,Gillespie, G.M. (deposition date: 2021-07-10, release date: 2022-07-27, Last modification date: 2024-10-09)

Primary citation

Walters, L.C.,Rozbesky, D.,Harlos, K.,Quastel, M.,Sun, H.,Springer, S.,Rambo, R.P.,Mohammed, F.,Jones, E.Y.,McMichael, A.J.,Gillespie, G.M.
Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes.
Cell Rep, 39:110959-110959, 2022

PubMed Abstract: MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8 T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the α2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting α2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination.

PubMed: 35705051
DOI: 10.1016/j.celrep.2022.110959

Experimental method

X-RAY DIFFRACTION (1.72 Å)