PDBsum entry: 1yjd

Immune system/signaling protein

PDB id: 1yjd

Contents

Protein chains

212 a.a. *

217 a.a. *

118 a.a. *

Ligands

NAG ×3

Waters ×203

* Residue conservation analysis

PDB id:

1yjd

Name:

Immune system/signaling protein

Title:

Crystal structure of human cd28 in complex with the fab frag mitogenic antibody (5.11a1)

Structure:

Fab fragment of 5.11a1 antibody light chain. Chain: l. Fab fragment of 5.11a1 antibody heavy chain. Chain: h. Fragment: igv and igc1 domains. T-cell-specific surface glycoprotein cd28. Chain: c. Fragment: extracellular region. Synonym: tp44.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Homo sapiens. Human. Organism_taxid: 9606. Gene: cd28. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.

Biol. unit:

Hexamer (from PDB file)

Resolution:

2.70Å R-factor: 0.239 R-free: 0.282

Authors:

E.J.Evans,R.M.Esnouf,R.Manso-Sancho,R.J.C.Gilbert,J.R.James, P.Sorensen,D.I.Stuart,S.J.Davis

Key ref:

E.J.Evans et al. (2005). Crystal structure of a soluble CD28-Fab complex. Nat Immunol, 6, 271-279. PubMed id: 15696168 DOI: 10.1038/ni1170

Date:

14-Jan-05 Release date: 15-Feb-05

Protein chain

No UniProt id for this chain

Protein chain

No UniProt id for this chain

Protein chain

P10747  (CD28_HUMAN) -  T-cell-specific surface glycoprotein CD28

Seq: 220 a.a.

Struc: 118 a.a.

 Gene Ontology (GO) functional annotation 

• Biochemical function: protein binding (1 term)

DOI no: 10.1038/ni1170

Nat Immunol 6:271-279 (2005)

PubMed id: 15696168

Crystal structure of a soluble CD28-Fab complex.

E.J.Evans, R.M.Esnouf, R.Manso-Sancho, R.J.Gilbert, J.R.James, C.Yu, J.A.Fennelly, C.Vowles, T.Hanke, B.Walse, T.Hünig, P.Sørensen, D.I.Stuart, S.J.Davis.

ABSTRACT

Naive T cell activation requires signaling by the T cell receptor and by nonclonotypic cell surface receptors. The most important costimulatory protein is the monovalent homodimer CD28, which interacts with CD80 and CD86 expressed on antigen-presenting cells. Here we present the crystal structure of a soluble form of CD28 in complex with the Fab fragment of a mitogenic antibody. Structural comparisons redefine the evolutionary relationships of CD28-related proteins, antigen receptors and adhesion molecules and account for the distinct ligand-binding and stoichiometric properties of CD28 and the related, inhibitory homodimer CTLA-4. Cryo-electron microscopy-based comparisons of complexes of CD28 with mitogenic and nonmitogenic antibodies place new constraints on models of antibody-induced receptor triggering. This work completes the initial structural characterization of the CD28-CTLA-4-CD80-CD86 signaling system.

Selected figure(s)

Figure 2.
Figure 2. Structure-based alignment of the CD28 and CTLA-4 extracellular domain sequences. Structures were aligned with SHP as shown in Figure 1d. The following features are highlighted: red, structurally equivalent residues conserved in all mammalian CD28 and CTLA-4 sequences; green and yellow, conserved CD28-specific (green) and CTLA-4-specific (yellow) sequences; gray, -strands; pale blue and orange, residues forming homodimeric contacts (pale blue) and 5.11A1 Fab-contacts (orange); maroon and dark blue, CTLA-4 residues that contact CD80 (maroon) and CD86 (dark blue).

Figure 5.
Figure 5. Proposed ligand- and 5.11A1 Fab complexes formed by putative CD28 homodimers. (a) Orthogonal views of the extracellular region of modeled CD80 -CD28 homodimer complexes. With SHP, each of the CTLA-4 monomers from the CTLA-4 -CD80 (PDB accession number 1i8l; dark blue) and CD86 -CTLA-4 (PDB accession number 1i85; pale blue) complexes was superimposed in turn on each of the monomers in the crystallographic CD28 homodimer (red). CD80 was then docked with CD28 according to the mode of ligand binding seen for the CTLA-4 monomer. (b) Superposition of CD28 and CTLA-4 homodimers as in Figure 4b, after the docking of CD80 to both molecules, as in a, based on the binding seen in PDB file 1i8l. (c) Two orthogonal views of the complex formed by the crystallographic sCD28 homodimer (red) and bivalently bound 5.11A1 Fab (green). The position of the mutation disrupting nonmitogenic antibody binding in rat CD28 is marked with light blue spheres. Top, horizontal line indicates approximate position of the membrane; the line of view is parallel to the membrane. Bottom, the line of view is toward the T cell.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Immunol (2005, 6, 271-279) copyright 2005.

Figures were selected by the author.