Crystal structure of the extracellular region of the human cell adhesion molecule CD2 at 2.5 A resolution.
BACKGROUND
The T-lymphocyte antigen CD2 is an adhesion molecule implicated in immune responses in vivo. The extracellular regions of the human and rat homologues of CD2 share only 45% sequence identity and bind different protein ligands. Comparison of the human and rat soluble CD2 (sCD2) structures should provide insights into the structural basis of cell surface recognition.


RESULTS
We therefore determined the crystal structure of a form of human sCD2 with single N-acetylglucosamine residues at each glycosylation site to 2.5 A resolution with an R-factor of 19.3%. It is composed of two immunoglobulin superfamily domains similar to those of rat sCD2, but the relative orientation of the domains in the two homologues differs by up to 20 degrees. An interaction involving the flat, highly charged, ligand binding GFCC'C" faces of crystallographically related human sCD2 molecules duplicates, in a different lattice, that observed in the rat sCD2 crystals.


CONCLUSIONS
Intramolecular flexibility appears to be a conserved feature of CD2. The head-to-head interaction between molecules represents a general model for interactions between adhesion molecules of this structural class. Ligand specificity may be influenced by the distribution of charged residues on the binding face.
Bodian
D L
DL
Laboratory of Molecular Biophysics, Oxford, UK.
Jones
E Y
EY
Harlos
K
K
Stuart
D I
DI
Davis
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018801:CD2 Antigens / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D013601:T-Lymphocytes / Q000737:chemistry
D018801:CD2 Antigens; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D007136:Immunoglobulins; D008024:Ligands; D011994:Recombinant Proteins