Glycosylation Modulates Human CD2-CD58 Adhesion via Conformational Adjustment.

Human CD2 is a transmembrane cell surface glycoprotein found on T lymphocytes and natural killer cells and plays important roles in immune recognition. The interaction between human CD2 and its counter receptor CD58 facilitates surface adhesion between helper T lymphocytes and antigen presenting cells as well as between cytolytic effectors and target cells. In this study, the molecular effect of glycosylation of CD2 on the structure and dynamics of the CD2-CD58 adhesion complex were examined via MD simulation to help understand the fundamental mechanism of glycosylation that controls CD2-CD58 adhesion. The present result and detailed analysis revealed that the binding interaction of human CD2-CD58 is dominated by three hot spots that form a binding triangle whose topology is critical for stable binding of CD2-CD58. Our study found that the conformation of human CD2, represented by the topology of this binding triangle, is significantly adjusted and steered by glycosylation toward a particular conformation that energetically stabilizes the CD2-CD58 complex. Thus, the fundamental mechanism of glycosylation of human CD2 is to promote CD2-CD58 binding by conformational adjustment of CD2. The current result and explanation are in excellent agreement with previous experiments and help elucidate the dynamical mechanism of glycosylation of human CD2.