PDBsum entry 1mi5

Immune system

PDB id

1mi5

Contents

			Protein chains

					277 a.a. *


					99 a.a. *


					201 a.a. *


					241 a.a. *

			Ligands

					PHE-LEU-ARG-GLY- ARG-ALA-TYR-GLY- LEU

			Waters ×232

* Residue conservation analysis

References listed in PDB file

Key reference

Title

A structural basis for the selection of dominant alphabeta t cell receptors in antiviral immunity.

Authors

L.Kjer-Nielsen, C.S.Clements, A.W.Purcell, A.G.Brooks, J.C.Whisstock, S.R.Burrows, J.Mccluskey, J.Rossjohn.

Ref.

Immunity, 2003, 18, 53-64. [DOI no: 10.1016/S1074-7613(02)00513-7]

PubMed id

12530975

Abstract

We have examined the basis for immunodominant or "public" TCR usage in an antiviral CTL response. Residues encoded by each of the highly selected genetic elements of an immunodominant clonotype recognizing Epstein-Barr virus were critical to the antigen specificity of the receptor. Upon recognizing antigen, the immunodominant TCR undergoes extensive conformational changes in the complementarity determining regions (CDRs), including the disruption of the canonical structures of the germline-encoded CDR1alpha and CDR2alpha loops to produce an enhanced fit with the HLA-peptide complex. TCR ligation induces conformational changes in the TCRalpha constant domain thought to form part of the docking site for CD3epsilon. These findings indicate that TCR immunodominance is associated with structural properties conferring receptor specificity and suggest a novel structural link between TCR ligation and intracellular signaling.



	Figure 1. Figure 1. Overview of the LC13 T Cell Receptor Complexed to HLA-B8/FLRGRAYGL(A) Ribbon representation of the LC13/HLA-B8/FLRGRAYGL complex. The α chain and β chain of LC13 TCR are shown in light red and blue, respectively. The HLA-B8 heavy chain and the β2-microglobulin domain are shown in light and darker green, respectively. The bound EBV peptide is in yellow, with the P7 Tyr residue shown in stick format.(B) A close-up of the interface, in an orthogonal view to (A), with the CDR regions color coded CDR1α, red; CDR2α, magenta; CDR3α, blue; CDR1β, orange; CDR2β, green; and CDR3β, cyan. Residues from CDR1 and CDR2 participating in polar contacts are highlighted.(C) Involvement of the publicly encoded regions that encompass CDR3 at the interface. The CDR3α loop residues and their corresponding amino acid sequence are color coded with the Vα backbone in red, N-region in dark blue, and Jα in dark green; CDR3β loop residues are coded with the Vβ backbone in orange; DβN-region light blue and Jβ light green. Residues P6 Ala, P7 Tyr, and P8 Gly of the FLRGRAYGL peptide are shown in yellow. Part of the HLA-B8 α2 helix has been removed to simplify the illustration. Selected residues from the HLA-B8 α1 and α2 helices are shown in gray.		Figure 4. Figure 4. Conformational Change in the Cα Domain that May Relate to a Conformational Switch for Intracellular Signaling in T Cells(A) The acidic ectodomain of CD3ε has been proposed to interact with the exposed electropositive surface of the A, B, E, and D strands of the Cβ domain shown in light green (Ghendler et al. 1998; Sun et al. 2001 and Wang et al. 1998). This cavity is bordered by the F-G loop of the Cβ domain. Conformational changes between unliganded (cyan) and liganded (red) states of this region are shown. Positively charged side chains (K121, K132, K136, K184, R190, and R230) projecting from Cα and Cβ are thought to further stabilize the docking of CD3ε into this cavity (Sun et al., 2001). Cα Lys132 swings toward the cavity upon ligation of LC13 while the whole of the A-B loop shifts to enlarge the cavity in the liganded complex.(B) Comparison of A-B loop structure in a number of different TCRs. Color coding of the A-B loop is as follows: unliganded LC13, cyan; liganded LC13, red; 2C, blue; A6 weak agonist, green; and the partially built loop of the B7 TCR, orange. The N15 A-B loop structure is not shown but resembles the 2C structure.

PROCHECK

	Headers