PDBsum entry: 1c16

Immune system

PDB id: 1c16

Contents

Protein chains

260 a.a. *

99 a.a. *

* Residue conservation analysis

PDB id:

1c16

Name:

Immune system

Title:

Crystal structure analysis of the gamma/delta t cell ligand t22

Structure:

Mhc-like protein t22. Chain: a, c, e, g. Protein (beta-2-microglobulin). Chain: b, d, f, h

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Tetramer (from PQS)

Resolution:

3.10Å R-factor: 0.284 R-free: 0.334

Authors:

C.Wingren,M.P.Crowley,M.Degano,Y.Chien,I.A.Wilson

Key ref:

C.Wingren et al. (2000). Crystal structure of a gammadelta T cell receptor ligand T22: a truncated MHC-like fold. Science, 287, 310-314. PubMed id: 10634787 DOI: 10.1126/science.287.5451.310

Date:

20-Jul-99 Release date: 26-Jan-00

Protein chains

Q31615  (Q31615_MOUSE) -  MHC class I H2-TL-27-129 mRNA (b haplotype), complete cds

Seq: 379 a.a.

Struc: 260 a.a.*

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin

Seq: 119 a.a.

Struc: 99 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (8 terms)
• Biological process: immune response (8 terms)
• Biochemical function: protein binding (1 term)

DOI no: 10.1126/science.287.5451.310

Science 287:310-314 (2000)

PubMed id: 10634787

Crystal structure of a gammadelta T cell receptor ligand T22: a truncated MHC-like fold.

C.Wingren, M.P.Crowley, M.Degano, Y.Chien, I.A.Wilson.

ABSTRACT

Murine T10 and T22 are highly related nonclassical major histocompatibility complex (MHC) class Ib proteins that bind to certain gammadelta T cell receptors (TCRs) in the absence of other components. The crystal structure of T22b at 3.1 angstroms reveals similarities to MHC class I molecules, but one side of the normal peptide-binding groove is severely truncated, which allows direct access to the beta-sheet floor. Potential gammadelta TCR-binding sites can be inferred from functional mapping of T10 and T22 point mutants and allelic variants. Thus, T22 represents an unusual variant of the MHC-like fold and indicates that gammadelta and alphabeta TCRs interact differently with their respective MHC ligands.

Selected figure(s)

Figure 1.
Fig. 1. Three-dimensional structures of T22^b and a classical MHC class I molecule (HLA-A2) (16, 17). (A) Ribbon diagram of the mouse T22^b heavy chain and human [2]M heterodimer. The two loop regions that adopt slightly different conformations in the four T22^b monomers of the asymmetric unit (22) are shown and colored yellow, cyan, magenta, and dark blue. No electron density was observed for residues 148 to 153 in molecule 3 (yellow) (22). Cysteine side chains (yellow) are shown in a ball-and-stick fashion (23). The Asn residues (86 and 150) of probable N-linked glycosylation sites are colored in black [(C) and (D) only]. (B) Ribbon diagram of HLA-A2. The molecule is color coded as for T22^b (C) Top view of the 1 and 2 domains of T22^b. (D) Top view of the 1 and 2 domains of HLA-A2. PROMOTIF was used to identify secondary structure elements (32). Figures 1, 2, and 3 were generated with MOLSCRIPT (32) and RASTER3D (32). N, NH[2]-terminal; C, COOH-terminal.

Figure 3.
Fig. 3. Top view of the 1 2 domains of T22^b. (A) Stereoview of the molecular surface of the 1 2 domains of T22^b. Electrostatic potentials were calculated in GRASP (32); positive potential ( 15 mv) is colored blue, neutral potential (0 mv) is colored gray, and negative potential ( 15 mv) is colored red. (B) Stereoview showing potential T cell-binding sites on the 1 2 domains of T22^b. G8 and KN6 recognize T10^b, T10^k, and T10^129 and T22^b and T22^129 (3, 4). T22^k and T22^d are not expressed on the cell surface (3, 35); thus, the following amino acid changes are tolerated: Asn59 Asp, Arg65 His, Gly100 Asp, Arg107 Gln, Asn127 Ser, His155 Gln, Asp159 His, Lys161 Glu, Ser162 Gly, and Leu167 Val (yellow) (33). In contrast, neither G8 nor KN6 recognizes T10^d. Antibody staining and surface immunoprecipitation indicate that this molecule is expressed on the cell surface (35). Three differences occur in T10^d as compared with T10^b and T22^b: Arg35 Leu, Asp58 Gly, and Phe^124 His (red). Although one of these mutations could affect the epitope for G8 and KN6, Asp58 is on the negatively charged NH[2]-terminal loop, whereas Phe^124 is on the exposed -sheet floor. In addition, KN6 can be stimulated by mutant T22^b molecules with single alanine substitutions at positions Arg6, Tyr9, Ile^23, Val25, or Gln115 (green), but not at positions Leu5, Tyr7, Leu95, Leu98, or Leu116 (purple) (30). Because Tyr7 normally forms a hydrogen bond with Gln63, a mutation at this position is more likely to affect the interaction between the TCR and T22 by secondary effects, such as local disruption of the T22 structure (hence, Tyr7 is colored in green). It is also unclear whether any of these mutant proteins were expressed on the cell surface (30). The limited sequence heterogeneity between T22 and T10 is located mainly in the exposed portion of the 1 2 platform; therefore, T10 is predicted to have a closely similar fold to T22. (C) Similar to (B), but now displaying the accessible molecular surface. (A) and (C) were generated with GRASP (32). The two possible binding sites for the TCR are shown by arrows and emphasize the data obtained from the allelic variants (red).

The above figures are reprinted by permission from the AAAs: Science (2000, 287, 310-314) copyright 2000.

Figures were selected by an automated process.