Structural basis for dimerization of ICAM-1 on the cell surface.

We have determined the 3.0 A crystal structure of the three C-terminal domains 3-5 (D3-D5) of ICAM-1. Combined with the previously known N-terminal two-domain structure (D1D2), a model of an entire ICAM-1 extracellular fragment has been constructed. This model should represent a general architecture of other ICAM family members, particularly ICAM-3 and ICAM-5. The observed intimate dimerization interaction at D4 and a stiff D4-D5 stem-like architecture provide a good structural explanation for the existence of preformed ICAM-1 cis dimers on the cell membrane. Together with another dimerization interface at D1, a band-like one-dimensional linear cluster of ICAM-1 on an antigen-presenting cell (APC) surface can be envisioned, which might explain the formation of an immunological synapse between an activated T cell and APC which is critical for T cell receptor signaling.