6GH1

HLA-E*01:03 in complex with Mtb44

6GH1 の概要

• エントリーDOI: 10.2210/pdb6gh1/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, Enoyl-[acyl-carrier-protein] reductase [NADH], ... (6 entities in total)
• 機能のキーワード: complex, histocompatibility antigen, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 179047.43

構造登録者

Walters, L.C.,Gillespie, G.M.,McMichael, A.J.,Rozbesky, D.,Jones, E.Y.,Harlos, K. (登録日: 2018-05-04, 公開日: 2018-08-08, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)