4MNQ

TCR-peptide specificity overrides affinity enhancing TCR-MHC interactions

4MNQ の概要

• エントリーDOI: 10.2210/pdb4mnq/pdb
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, Telomerase reverse transcriptase, ... (8 entities in total)
• 機能のキーワード: surface plasmon resonance (spr); biacoretm; peptide-major histocompatibility complex (pmhc): t-cell receptor (tcr), t-cells; high affinity tcr, two-step binding, adoptive therapy, immunoglobulin, adaptive immune response, 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: P01892; Secreted . Note=(Microbial infection) In the presence of M: P61769; Nucleus, nucleolus : O14746; Membrane ; Single-pass membrane protein : P01850
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 94569.98

構造登録者

Rizkallah, P.J.,Cole, D.K.,Sewell, A.K.,Jakobsen, B.K. (登録日: 2013-09-11, 公開日: 2013-11-13, 最終更新日: 2024-10-16)

主引用文献

Cole, D.K.,Miles, K.M.,Madura, F.,Holland, C.J.,Schauenburg, A.J.,Godkin, A.J.,Bulek, A.M.,Fuller, A.,Akpovwa, H.J.,Pymm, P.G.,Liddy, N.,Sami, M.,Li, Y.,Rizkallah, P.J.,Jakobsen, B.K.,Sewell, A.K.
T-cell receptor (TCR)-peptide specificity overrides affinity-enhancing TCR-major histocompatibility complex interactions.
J.Biol.Chem., 289:628-638, 2014

PubMed Abstract: αβ T-cell receptors (TCRs) engage antigens using complementarity-determining region (CDR) loops that are either germ line-encoded (CDR1 and CDR2) or somatically rearranged (CDR3). TCR ligands compose a presentation platform (major histocompatibility complex (MHC)) and a variable antigenic component consisting of a short "foreign" peptide. The sequence of events when the TCR engages its peptide-MHC (pMHC) ligand remains unclear. Some studies suggest that the germ line elements of the TCR engage the MHC prior to peptide scanning, but this order of binding is difficult to reconcile with some TCR-pMHC structures. Here, we used TCRs that exhibited enhanced pMHC binding as a result of mutations in either CDR2 and/or CDR3 loops, that bound to the MHC or peptide, respectively, to dissect the roles of these loops in stabilizing TCR-pMHC interactions. Our data show that TCR-peptide interactions play a strongly dominant energetic role providing a binding mode that is both temporally and energetically complementary with a system requiring positive selection by self-pMHC in the thymus and rapid recognition of non-self-pMHC in the periphery.

PubMed: 24196962
DOI: 10.1074/jbc.M113.522110

実験手法

X-RAY DIFFRACTION (2.742 Å)