PDBsum entry 2dru

Immune system

PDB id: 2dru

Contents

Protein chain

180 a.a. *

Ligands

NAG ×3

GOL ×5

Waters ×42

* Residue conservation analysis

PDB id:

2dru

Name:

Immune system

Title:

Crystal structure and binding properties of the cd2 and cd244 (2b4) binding protein, cd48

Structure:

Chimera of cd48 antigen and t-cell surface antigen cd2. Chain: a. Fragment: domain 1, cd2 binding domain. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: cho cells

Resolution:

2.60Å R-factor: 0.214 R-free: 0.271

Authors:

E.J.Evans,S.Ikemizu,S.J.Davis

Key ref:

E.J.Evans et al. (2006). Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding protein, CD48. J Biol Chem, 281, 29309-29320. PubMed id: 16803907 DOI: 10.1074/jbc.M601314200

Date:

15-Jun-06 Release date: 04-Jul-06

Protein chain

P08921  (CD2_RAT) -  T-cell surface antigen CD2 from Rattus norvegicus

Seq: 344 a.a.

Struc: 180 a.a.*

Protein chain

P10252  (CD48_RAT) -  CD48 antigen from Rattus norvegicus

Seq: 240 a.a.

Struc: 180 a.a.*

* PDB and UniProt seqs differ at 146 residue positions (black crosses)

DOI no: 10.1074/jbc.M601314200

J Biol Chem 281:29309-29320 (2006)

PubMed id: 16803907

Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding protein, CD48.

E.J.Evans, M.A.Castro, R.O'Brien, A.Kearney, H.Walsh, L.M.Sparks, M.G.Tucknott, E.A.Davies, A.M.Carmo, P.A.van der Merwe, D.I.Stuart, E.Y.Jones, J.E.Ladbury, S.Ikemizu, S.J.Davis.

ABSTRACT

The structural analysis of surface proteins belonging to the CD2 subset of the immunoglobulin superfamily has yielded important insights into transient cellular interactions. In mice and rats, CD2 and CD244 (2B4), which are expressed predominantly on T cells and natural killer cells, respectively, bind the same, broadly expressed ligand, CD48. Structures of CD2 and CD244 have been solved previously, and we now present the structure of the receptor-binding domain of rat CD48. The receptor-binding surface of CD48 is unusually flat, as in the case of rat CD2, and shares a high degree of electrostatic complementarity with the equivalent surface of CD2. The relatively simple arrangement of charged residues and this flat topology explain why CD48 cross-reacts with CD2 and CD244 and, in rats, with the CD244-related protein, 2B4R. Comparisons of modeled complexes of CD2 and CD48 with the complex of human CD2 and CD58 are suggestive of there being substantial plasticity in the topology of ligand binding by CD2. Thermodynamic analysis of the native CD48-CD2 interaction indicates that binding is driven by equivalent, weak enthalpic and entropic effects, in contrast to the human CD2-CD58 interaction, for which there is a large entropic barrier. Overall, the structural and biophysical comparisons of the CD2 homologues suggest that the evolutionary diversification of interacting cell surface proteins is rapid and constrained only by the requirement that binding remains weak and specific.

Selected figure(s)

Figure 3.
FIGURE 3. The ligand binding face of rat CD48. The surface of the V-set domain of rCD48 is shown oriented to reveal the ligand-binding GFCC'C'' face of the protein, as in Fig. 2. A, the surfaces of residues whose mutation disrupts CD2 binding are colored red and labeled, whereas those whose mutation has no effect are colored green. B, the surface is uncolored to reveal its flatness; the outline of the CD2 binding surface (as seen in A) is shown. C, the surface is colored by its native electrostatic potential calculated at neutral pH; blue represents positive potential, white represents neutral, and red represents negative potential contoured at ±8.5 kT.

Figure 5.
FIGURE 5. Modeling the rCD48-rCD2 complex. A, two orthogonal views of a ribbon representation of the likely complex formed between the full extracellular domains of rat CD2 (blue) and rat CD48 (green, modeled on cCD48). B, expanded view of the interface, with the side chains of the residues most likely to be involved in the interaction shown as ball-and-stick representations. Hydrogen bonds are shown as dashed red lines. C, comparison of the modeled rat CD2-CD48 complex (left) with the solved human CD2-CD58 complex (right, CD58 in red). The solvent-accessible molecular surface of the separate proteins is shown semi-transparently over a representation of their secondary structure to illustrate the complementarity of the binding surfaces.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 29309-29320) copyright 2006.

Figures were selected by the author.