PDBsum entry: 1akj

Complex (mhc i/peptide/cd8)

PDB id: 1akj

Contents

Protein chains

276 a.a. *

98 a.a. *

114 a.a. *

Ligands

ILE-LEU-LYS-GLU-PRO-VAL-HIS-GLY-VAL

Waters ×108

* Residue conservation analysis

PDB id:

1akj

Name:

Complex (mhc i/peptide/cd8)

Title:

Complex of the human mhc class i glycoprotein hla-a2 and the t cell coreceptor cd8

Structure:

Mhc class i histocompatibility antigen (hla- a 0201) (Alpha chain). Chain: a. Fragment: extracellular domain. Synonym: hla-a2, hla-a 0201. Engineered: yes. Beta 2-microglobulin. Chain: b. Fragment: extracellular domain.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Gene: beta-2-microglobulin. Expressed in: escherichia coli. Expression_system_taxid: 562. Human immunodeficiency virus. Organism_taxid: 12721.

Biol. unit:

Pentamer (from PQS)

Resolution:

2.65Å R-factor: 0.206 R-free: 0.276

Authors:

J.Tormo,D.I.Stuart,E.Y.Jones

Key ref:

G.F.Gao et al. (1997). Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature, 387, 630-634. PubMed id: 9177355 DOI: 10.1038/42523

Date:

21-May-97 Release date: 17-Sep-97

Protein chain

P01892  (1A02_HUMAN) -  HLA class I histocompatibility antigen, A-2 alpha chain

Seq: 365 a.a.

Struc: 276 a.a.

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin

Seq: 119 a.a.

Struc: 98 a.a.

Protein chains

P01732  (CD8A_HUMAN) -  T-cell surface glycoprotein CD8 alpha chain

Seq: 235 a.a.

Struc: 114 a.a.

 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: 10.1038/42523

Nature 387:630-634 (1997)

PubMed id: 9177355

Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2.

G.F.Gao, J.Tormo, U.C.Gerth, J.R.Wyer, A.J.McMichael, D.I.Stuart, J.I.Bell, E.Y.Jones, B.K.Jakobsen.

ABSTRACT

The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions.

Selected figure(s)

Figure 1.
Figure 1 The structure of the CD8 /HLA-A2/peptide complex and the interaction surfaces. a, Stereo view of the complex. The HLA-A2 heavy chain (green), [2]m (gold), CD8 -1 (red) and CD8 -2 (blue) are depicted schematically, and the pol peptide (ILKEPVHGV) is shown in white as a ball-and-stick representation. Secondary structure assignments are from program DSSP24, modified in places to accord with previous reports. This orientation defines a standard view for b-d. b, The interaction surfaces. The solvent-accessible surface of CD8 (calculated in the absence of the rest of the complex by the program VOLUMES; R. Esnouf, unpublished) is shown as a semi-transparent surface. The regions depicted in close up in c and d are indicated by a circle and a rectangle, respectively. The polypeptide chains are represented schematically as in a but the view is slightly rotated about the horizontal. c, The HLA-A2 3/CD8 interaction surface. d, The HLA-A2 2, [2]m and CD8 -1 interaction surface. Components of this figure and of Fig. 2 were drawn using programs MOLSCRIPT25 (with modifications by R. Esnouf) and RASTER3D^26;

Figure 2.
Figure 2 Structural comparisons and models. a, Range of positional variation for the MHC class I 3 domain. Equivalent C atoms for the MHC heavy-chain residues 1-174 were used to generate pairwise superpositions taking residues from the HLA-B53/ls6 complex as the common reference set27. C traces for the heavy chains and [2]m from isolated MHC class I/peptide complexes (PDB codes: 1hhg, 1hhh, 1hhi, 1hhj, 1hhk, 1hsb, 1mhc, 1vac, 1vad, 2clr, 2vag, 2vab and 3hla) are shown in yellow; the HLA-A2 heavy chain and [2]m from the HLA-A2/TCR complex5 are coloured red, and those from the CD8 /HLA-A2/peptide complex are coloured blue. The peptide of the CD8 /HLA-A2/peptide complex is shown in white. b, Loss of the CD8 binding conformation for the 223-229 loop in HLA-Aw68. Equivalent C atoms were used to generate superpositions for the 3 domains of uncomplexed HLA-A2 (yellow), HLA-Aw68 (green) and HLA-A2 when complexed with CD8 (blue). For clarity, the right-hand-side close up is rotated about the vertical relative to the standard view. The hydrogen bond defining the turn between residues 224-227 is shown as a broken line and is conserved in both the isolated and complexed HLA-A2 structures but is lost for the distorted loop conformation of HLA-Aw68. This turn is central to the interaction of 3 and CD8 (Fig. 1c). c, A model for CD8 and TCR binding to MHC class I. The putative position of the TCR relative to the CD8 /HLA-A2/peptide complex is based on a superposition of the TCR/Tax/HLA-A2 complex5 generated using equivalent C atoms for HLA-A2 residues 1-174. The HLA-A2 heavy chain (green), [2]m (gold), CD8 -1 (red) and CD8 -2 (blue) are depicted schematically, and the pol peptide is shown in white as a ball-and-stick representation. The superposed TCR (variable domain) and (variable and constant domains) are shown in light and dark pink, respectively. The approximate positions of the T-cell and antigen-presenting cell surfaces are indicated by broad broken lines. Structural superpositions were performed using the program SHP28.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1997, 387, 630-634) copyright 1997.