5KNM

Human leukocyte antigen F (HLA-F) presents peptides and regulates immunity through interactions with NK-cell receptors

5KNM の概要

• エントリーDOI: 10.2210/pdb5knm/pdb
• 関連するPDBエントリー: 5IUE
• 分子名称: cDNA FLJ39643 fis, clone SMINT2004023, highly similar to HLA class I histocompatibility antigen, alphachain F, Beta-2-microglobulin, Leukocyte immunoglobulin-like receptor subfamily B member 1, ... (5 entities in total)
• 機能のキーワード: mhc-ib, immune system, peptide binding protein, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83362.59

構造登録者

Dulberger, C.L.,Adams, E.J. (登録日: 2016-06-28, 公開日: 2017-06-14, 最終更新日: 2024-10-16)

主引用文献

Dulberger, C.L.,McMurtrey, C.P.,Holzemer, A.,Neu, K.E.,Liu, V.,Steinbach, A.M.,Garcia-Beltran, W.F.,Sulak, M.,Jabri, B.,Lynch, V.J.,Altfeld, M.,Hildebrand, W.H.,Adams, E.J.
Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors.
Immunity, 46:1018-1029.e7, 2017

PubMed Abstract: Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement. Our in vitro studies confirm that NKRs differentiate between peptide-bound and peptide-free HLA-F. The complex structure of peptide-loaded βm-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as βm, thus precluding binding to HLA-F OCs. These findings provide a biochemical framework to understand how HLA-F could regulate immunity via interactions with NKRs.

PubMed: 28636952
DOI: 10.1016/j.immuni.2017.06.002

実験手法

X-RAY DIFFRACTION (3.3 Å)