3L3I

Crystal structure of HLA-B*4402 in complex with the F7A mutant of a self-peptide derived from DPA*0201

3L3I の概要

• エントリーDOI: 10.2210/pdb3l3i/pdb
• 関連するPDBエントリー: 1M6O 3L3D 3L3G 3L3J 3L3K
• 分子名称: HLA class I histocompatibility antigen, B-44 alpha chain, Beta-2-microglobulin, peptide from HLA-DPA1 protein, ... (5 entities in total)
• 機能のキーワード: immunoglobulin domain, immune response, major histocompatibility complex class i, mhc-i peptide complex, altered peptide ligand, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P30481; Secreted: P61769
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 45110.86

構造登録者

Theodossis, A.,Ely, L.K.,Rossjohn, J. (登録日: 2009-12-17, 公開日: 2010-03-16, 最終更新日: 2024-10-09)

主引用文献

Theodossis, A.,Guillonneau, C.,Welland, A.,Ely, L.K.,Clements, C.S.,Williamson, N.A.,Webb, A.I.,Wilce, J.A.,Mulder, R.J.,Dunstone, M.A.,Doherty, P.C.,McCluskey, J.,Purcell, A.W.,Turner, S.J.,Rossjohn, J.
Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition
Proc.Natl.Acad.Sci.USA, 107:5534-5539, 2010

PubMed Abstract: Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered to function as a series of "independent pegs" that either anchor the peptide (p) to the MHC-I and/or interact with the spectrum of alphabeta-T-cell receptors (TCRs) specific for the pMHC-I epitope in question. Mining of the extensive pMHC-I structural database established that many self- and viral peptides show extensive and direct interresidue interactions, an unexpected finding that has led us to the idea of "constrained" peptides. Mutational analysis of two constrained peptides (the HLA B44 restricted self-peptide (B44DPalpha-EEFGRAFSF) and an H2-D(b) restricted influenza peptide (D(b)PA, SSLENFRAYV) demonstrated that the conformation of the prominently exposed arginine in both peptides was governed by interactions with MHC-I-orientated flanking residues from the peptide itself. Using reverse genetics in a murine influenza model, we revealed that mutation of an MHC-I-orientated residue (SSLENFRAYV --> SSLENARAYV) within the constrained PA peptide resulted in a diminished cytotoxic T lymphocyte (CTL) response and the recruitment of a limited pMHC-I specific TCR repertoire. Interactions between individual peptide positions can thus impose fine control on the conformation of pMHC-I epitopes, whereas the perturbation of such constraints can lead to a previously unappreciated mechanism of viral escape.

PubMed: 20212169
DOI: 10.1073/pnas.1000032107

実験手法

X-RAY DIFFRACTION (1.7 Å)