Peptide-dependent conformational fluctuation determines the stability of the human leukocyte antigen class I complex

Saeko Yanaka, Takamasa Ueno, Yi Shi, Jianxun Qi, George F. Gao, Kouhei Tsumoto, Kenji Sugase

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

In immune-mediated control of pathogens, human leukocyte antigen (HLA) class I presents various antigenic peptides to CD8+ T-cells. Long-lived peptide presentation is important for efficient antigen-specific T-cell activation. Presentation time depends on the peptide sequence and the stability of the peptide-HLA complex (pHLA). However, the determinant of peptide-dependent pHLA stability remains elusive. Here, to reveal the pHLA stabilization mechanism, we examined the crystal structures of an HLA class I allomorph in complex with HIV derived peptides and evaluated site-specific conformational fluctuations using NMR. Although the crystal structures of various pHLAs were almost identical independent of the peptides, fluctuation analyses identified a peptide-dependent minor state that would be more tightly packed toward the peptide. The minor population correlated well with the thermostability and cell surface presentation of pHLA, indicating that this newly identified minor state is important for stabilizing the pHLA and facilitating T-cell recognition.

Original languageEnglish
Pages (from-to)24680-24690
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number35
DOIs
Publication statusPublished - 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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