Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study.

• 影响指数: 7.666
• 发表时间: 07 2019 13
• 来源期刊: Cells
• DOI: 10.3390/cells8070720
• PMID: 31337065
• 文章类型: Journal Article
• 中科院分区: Q4
• 方向: 生物
• 作者列表: Karch R,Stocsits C,Ilieva N,Schreiner W

关键词: T-cell receptor; antigen; domain movements; major histocompatibility complex; molecular dynamics simulation

Mesh: Binding Sites; Humans; Major Histocompatibility Complex; Molecular Dynamics Simulation; Peptides / chemistry; Protein Binding; Protein Conformation; Receptors, Antigen, T-Cell, alpha-beta / chemistry

Abstract

The interaction of antigenic peptides (p) and major histocompatibility complexes (pMHC) with T-cell receptors (TCR) is one of the most important steps during the immune response. Here we present a molecular dynamics simulation study of bound and unbound TCR and pMHC proteins of the LC13-HLA-B*44:05-pEEYLQAFTY complex to monitor differences in relative orientations and movements of domains between bound and unbound states of TCR-pMHC. We generated local coordinate systems for MHC α1- and MHC α2-helices and the variable T-cell receptor regions TCR Vα and TCR Vβ and monitored changes in the distances and mutual orientations of these domains. In comparison to unbound states, we found decreased inter-domain movements in the simulations of bound states. Moreover, increased conformational flexibility was observed for the MHC α2-helix, the peptide, and for the complementary determining regions of the TCR in TCR-unbound states as compared to TCR-bound states.