Crystal structure at 2.8 Å resolution of a soluble form of the cell adhesion molecule CD2

Jones EY, Davis SJ, Williams AF, Harlos K, Stuart DI. (1992), Nature. 360, 232-9

Abstract

The crystal structure of a soluble form of the T lymphocyte antigen CD2 provides the first complete view of the extracellular region of a cell adhesion molecule. The topology of the molecule, which comprises two immunoglobulin-like domains, is the same as that of the first two domains of CD4 but the relative domain orientation is altered by a fairly flexible linker region. The putative ligand-binding beta-sheet forms a flat surface towards the top of the molecule. Crystal contacts between these surfaces suggest a plausible model for the adhesive interaction.

Key figure: The structure of sCD2

The orientation of sCD2 is chosen relative to a cell surface assumed to lie at the bottom of the illustration in the plane normal to the vertical. a, Schematic diagram of the polypeptide fold (program RIBBON⁴⁷). Several of the loops in domain 1 are flexible; r.m.s. deviations between main-chain atoms for the two copies of sCD2 exceed 1.0 Å for residues 20-26, 34-37, 44-47, 70-71 and 85-86. Bifurcation of the electron density at Gly4 indicates a degree of structural fluidity in the first 4 residues of the polypeptide chain. The alternative conformation extends away from the molecule, stabilized by crystal contacts. The disulphide bonds are indicated in green (1) Cys 117 and 157; (2) Cys 110 and 174. Asparagine residues providing N-linked oligosaccharide sites are indicated in red. N67 lies on the EF loop at the bottom of domain 1, N77 in strand F is orientated towards the bottom of the F and G strands. N84 at the tip of the FG loop points back, above the BC loop. N112 lies on the AB loop at the base of domain 2. b, α-Carbon trace superpositions for CD2 and CD4. Two orthogonal views are shown. The molecules are matched on CD2 domain 2. CD2, green; CD4, red. c, α-Carbon trace superpositions for CD2, CD4 and Fab NEW light chain. The molecules are matched on CD2 domain 2. Note the Fab domain 1 is flipped over by some 90° with respect to CD2 domain 1. CD2, green; CD4, red and NEW, blue. d, Linker region. Residues involved in hydrophobic and van der Waals interactions at the domain interface are indicated in green and include W7, A9, L10, E99, M100, R162 and V163, with R70 forming a salt bridge to E99. This type of link may be characterized by the stretch of apolar residues in the N-terminal β-strand A and a hydrogen bond network in domain 2 mediated by Ser-X-Pro at the start of β-strand A combined with Asn 161 and Ser 164 at the end of β-strand F and start of G (residues in red). e, Solid sphere representation (van der Waals surface). The colour coding accords with the electrostatic potential computed with DELPHI⁴⁸ (in collaboration with C. Edge) at neutral pH; blue represents positive potential, red negative, and white neutral. The orientation is almost orthogonal to that in a. The surface of the domain 1 GFCC’C” sheet is indicated by ‘A’ and the domain 2 GFCC’ sheet by ‘B’. f, Domain 1 GFCC’C” sheet. Colour coding as in e. The view is along the normal to the β-sheet surface as indicated by the line in e.