BACKGROUND: CD2, a T-cell specific surface glycoprotein, is critically important for mediating adherence of T cells to antigen-presenting cells or target cells. Domain 1 of human CD2 is responsible for cell adhesion, binding to CD58 (LFA-3) expressed on the cell to which the T cell binds. Human CD2 domain 1 requires N-linked carbohydrate to maintain its native conformation and ability to bind CD58. In contrast, rat CD2 does not require N-linked carbohydrate, and binds to a different ligand, CD48. RESULTS: The three-dimensional structure of the glycosylated form of domain 1 of human CD2 has been determined by NMR spectroscopy. The overall structure resembles the typical beta-barrel of an immunoglobulin variable domain. Nuclear Overhauser enhancement contacts between the protein and the N-linked glycan have been tentatively identified. CONCLUSION: Based on our results, we propose a model showing how the N-linked glycan might be positioned in the human CD2 domain 1 structure. The model provides an explanation for the observed instability of deglycosylated human CD2, and allows residues that are important for CD58 binding to be differentiated from those affecting conformational stability via interactions with the glycan.
BACKGROUND:CD2, a T-cell specific surface glycoprotein, is critically important for mediating adherence of T cells to antigen-presenting cells or target cells. Domain 1 of humanCD2 is responsible for cell adhesion, binding to CD58 (LFA-3) expressed on the cell to which the T cell binds. HumanCD2 domain 1 requires N-linked carbohydrate to maintain its native conformation and ability to bind CD58. In contrast, ratCD2 does not require N-linked carbohydrate, and binds to a different ligand, CD48. RESULTS: The three-dimensional structure of the glycosylated form of domain 1 of humanCD2 has been determined by NMR spectroscopy. The overall structure resembles the typical beta-barrel of an immunoglobulin variable domain. Nuclear Overhauser enhancement contacts between the protein and the N-linked glycan have been tentatively identified. CONCLUSION: Based on our results, we propose a model showing how the N-linked glycan might be positioned in the humanCD2 domain 1 structure. The model provides an explanation for the observed instability of deglycosylated humanCD2, and allows residues that are important for CD58 binding to be differentiated from those affecting conformational stability via interactions with the glycan.
Authors: Jining Liu; Jinfa Ying; Vincent T K Chow; Victor J Hruby; Seetharama D Satyanarayanajois Journal: J Med Chem Date: 2005-10-06 Impact factor: 7.446
Authors: A R Arulanandam; J M Withka; D F Wyss; G Wagner; A Kister; P Pallai; M A Recny; E L Reinherz Journal: Proc Natl Acad Sci U S A Date: 1993-12-15 Impact factor: 11.205