PDBsum entry 1hxm

Immune system

PDB id

1hxm

Contents

			Protein chains

					206 a.a. *


					230 a.a. *

			Ligands

					SO4 ×2

			Waters ×54

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of a human gammadelta t-Cell antigen receptor.

Authors

T.J.Allison, C.C.Winter, J.J.Fournié, M.Bonneville, D.N.Garboczi.

Ref.

Nature, 2001, 411, 820-824. [DOI no: 10.1038/35081115]

PubMed id

11459064

Abstract

T-cell antigen receptors composed of gamma and delta polypeptide chains (gammadelta TCRs) can directly recognize antigens in the form of intact proteins or non-peptide compounds, unlike alphabeta TCRs, which recognize antigens bound to major histocompatibility complex molecules (MHC). About 5% of peripheral blood T cells bear gammadelta TCRs, most of which recognize non-peptide phosphorylated antigens. Here we describe the 3.1 A resolution structure of a human gammadelta TCR from a T-cell clone that is phosphoantigen-reactive. The orientation of the variable (V) and constant (C) regions of the gammadelta TCR is unique when compared with alphabeta TCRs or antibodies, and results from an unusually small angle between the Vgamma and Cgamma domains. The complementarity-determining regions (CDRs) of the V domains exhibit a chemically reasonable binding site for phosphorylated antigens, providing a possible explanation for the canonical usage of the Vgamma9 and Vdelta2 gene segments by phosphoantigen-reactive receptors. Although the gammadelta TCR V domains are similar in overall structure to those of alphabeta TCRs, gammadelta TCR C domains are markedly different. Structural differences in Cgamma and Cdelta, and in the location of the disulphide bond between them, may enable gammadelta TCRs to form different recognition/signalling complexes than alphabeta TCRs.



	Figure 1. Figure 1: Views of the G115 V bold gamma-9V delta-2 TCR. a, View of V and C (red) and V and C (gold) domains. CDR loops are at the top. b, View after a 90� rotation around the vertical axis. The nine -strands of the V domains are labelled A -G, including A', C', and C". The seven -strands of the C domains are labelled A -G. In each domain, strands A, B, E, and D form one -sheet, and strands G, F and C (including A', C' and C" in the V domains) form the other sheet. The V -V interface involves the A'GFCC'C" -sheets. The C -C [139]delta interface involves the ABED [140]beta -sheets.		Figure 3. Figure 3: Surface representations of G115. a, The surface of G115 is coloured by CDR loops (CDR1, blue; CDR2, green; HV4, pink; and CDR3, red). b, 3-formyl-1-butyl-pyrophosphate is shown as a drawing and as a space-filling model (at the same scale as G115 in a and c). c, The surface potential of G115 is colour-coded from red (-10 kT) to blue (+10 kT). The top of the molecule, containing the CDR loops, is facing the viewer. The cleft between the two CDR3 loops contains positively charged patches (blue), which line the phosphoantigen-binding site. d, Enlarged view of the cleft shows the location of charged (negative in red; positive in blue), hydrophobic (yellow) and polar (green) residues.