STRUCTURE OF THE GLYCOSYLATED ADHESION DOMAIN OF HUMAN T-LYMPHOCYTE GLYCOPROTEIN CD2

Background: CD2, a T-cell specific surface glycoprotein, is critically important for mediating adherence of T cells to antigen-presenting ce lls or target cells. Domain 1 of human CD2 is responsible for cell adh esion, binding to CD58 (LFA-3) expressed on the cell to which the T ce ll binds. Human CD2 domain 1 requires N-linked carbohydrate to maintai n its native conformation and ability to bind CD58. In contrast, rat C D2 does not require N-linked carbohydrate, and binds to a different li gand, CD48. Results: The three-dimensional structure of the glycosylat ed form of domain 1 of human CD2 has been determined by NMR spectrosco py. The overall structure resembles the typical beta-barrel of an immu noglobulin variable domain. Nuclear Overhauser enhancement contacts be tween the protein and the N-linked glycan have been tentatively identi fied. Conclusion: Based on our results, we propose a model showing how the N-linked glycan might be posi tioned in the human CD2 domain 1 st ructure. The model provides an explanation for the observed instabilit y of deglycosylated human CD2, and allows residues that are important for CD58 binding to be differentiated from those affecting conformatio nal stability via interactions with the glycan.