6KWL

Crystal structure of pSLA-1*0401(R156A) complex with FMDV-derived epitope MTAHITVPY

6KWL の概要

• エントリーDOI: 10.2210/pdb6kwl/pdb
• 分子名称: MHC class I antigen, Beta-2-microglobulin, peptide, ... (4 entities in total)
• 機能のキーワード: mhc class i structure, a single-amino acid mutation, peptide motifs, random peptide library, structural protein
• 由来する生物種: Sus scrofa (Pig); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44061.01

構造登録者

Wei, X.H.,Wang, S.,Zhang, N.Z.,Xia, C. (登録日: 2019-09-07, 公開日: 2020-09-09, 最終更新日: 2023-11-22)

主引用文献

Wei, X.,Wang, S.,Li, Z.,Li, Z.,Qu, Z.,Wang, S.,Zou, B.,Liang, R.,Xia, C.,Zhang, N.
Peptidomes and Structures Illustrate Two Distinguishing Mechanisms of Alternating the Peptide Plasticity Caused by Swine MHC Class I Micropolymorphism.
Front Immunol, 12:592447-592447, 2021

PubMed Abstract: The micropolymorphism of major histocompatibility complex class I (MHC-I) can greatly alter the plasticity of peptide presentation, but elucidating the underlying mechanism remains a challenge. Here we investigated the impact of the micropolymorphism on peptide presentation of swine MHC-I (termed swine leukocyte antigen class I, SLA-I) molecules immunopeptidomes that were determined by our newly developed random peptide library combined with the mass spectrometry (MS) sequencing method (termed RPLD-MS) and the corresponding crystal structures. The immunopeptidomes of SLA-1*04:01, SLA-1*13:01, and their mutants showed that mutations of residues 156 and 99 could expand and narrow the ranges of peptides presented by SLA-I molecules, respectively. R156A mutation of SLA-1*04:01 altered the charge properties and enlarged the volume size of pocket D, which eliminated the harsh restriction to accommodate the third (P3) anchor residue of the peptide and expanded the peptide binding scope. Compared with 99 of SLA-1*0401, 99 of SLA-1*13:01 could not form a conservative hydrogen bond with the backbone of the P3 residues, leading to fewer changes in the pocket properties but a significant decrease in quantitative of immunopeptidomes. This absent force could be compensated by the salt bridge formed by P1-E and 170. These data illustrate two distinguishing manners that show how micropolymorphism alters the peptide-binding plasticity of SLA-I alleles, verifying the sensitivity and accuracy of the RPLD-MS method for determining the peptide binding characteristics of MHC-I and helping to more accurately predict and identify MHC-I restricted epitopes.

PubMed: 33717070
DOI: 10.3389/fimmu.2021.592447

実験手法

X-RAY DIFFRACTION (1.8 Å)