 |
PDBsum entry 2dru
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
2dru
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure and binding properties of the cd2 and cd244 (2b4)-Binding protein, Cd48.
|
|
|
Authors
|
|
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.
|
|
|
Ref.
|
|
J Biol Chem, 2006,
281,
29309-29320.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
