6GGM

HLA-E*01:03 in complex with the Mtb44 peptide variant: Mtb44*P2-Phe.

Summary for 6GGM

• Entry DOI: 10.2210/pdb6ggm/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Mtb44*P2-Phe peptide variant (ARG-PHE-PRO-ALA-LYS-ALA-PRO-LEU-LEU), ... (6 entities in total)
• Functional Keywords: complex, histocompatibility antigen, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 89820.68

Authors

Walters, L.C.,Gillespie, G.M.,McMichael, A.J.,Rozbesky, D.,Jones, E.Y.,Harlos, K. (deposition date: 2018-05-03, release date: 2018-08-08, Last modification date: 2024-10-16)

Primary citation

Walters, L.C.,Harlos, K.,Brackenridge, S.,Rozbesky, D.,Barrett, J.R.,Jain, V.,Walter, T.S.,O'Callaghan, C.A.,Borrow, P.,Toebes, M.,Hansen, S.G.,Sacha, J.,Abdulhaqq, S.,Greene, J.M.,Fruh, K.,Marshall, E.,Picker, L.J.,Jones, E.Y.,McMichael, A.J.,Gillespie, G.M.
Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding.
Nat Commun, 9:3137-3137, 2018

PubMed Abstract: Through major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However, Mycobacteria tuberculosis (Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8 T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo.

PubMed: 30087334
DOI: 10.1038/s41467-018-05459-z

Experimental method

X-RAY DIFFRACTION (2.734 Å)