6J2A

The structure of HLA-A*3003/NP44

6J2A の概要

• エントリーDOI: 10.2210/pdb6j2a/pdb
• 分子名称: HLA-A*3003, Beta-2-microglobulin, NP44, ... (4 entities in total)
• 機能のキーワード: the structure of hla-a*3003/np44, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44413.10

構造登録者

Zhu, S.Y.,Liu, K.F.,Chai, Y.,Ding, C.M.,Lv, J.X.,Gao, F.G.,Lou, Y.L.,Liu, W.J. (登録日: 2018-12-31, 公開日: 2019-09-25, 最終更新日: 2024-10-23)

主引用文献

Zhu, S.,Liu, K.,Chai, Y.,Wu, Y.,Lu, D.,Xiao, W.,Cheng, H.,Zhao, Y.,Ding, C.,Lyu, J.,Lou, Y.,Gao, G.F.,Liu, W.J.
Divergent Peptide Presentations of HLA-A*30 Alleles Revealed by Structures With Pathogen Peptides.
Front Immunol, 10:1709-1709, 2019

PubMed Abstract: Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A30:01 and -A30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A30:01 and -A30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A30:01, and -A30:03 were similar to those of HLA-A11:01 in the A3 supertype. However, HLA-A30:03, but not -A30:01, also showed binding with the HLA01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A30:01 and -A30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A30:01 and -A30:03. Interchanging residue 77 between HLA-A30:01 and HLA-A30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.

PubMed: 31396224
DOI: 10.3389/fimmu.2019.01709

実験手法

X-RAY DIFFRACTION (1.4 Å)