Abstract
The immunoglobulin domain is a module found in vertebrates and invertebrates. Its ability to form linear rods when deployed in series, combined with its propensity to bind specifically to other proteins has made it ideal for building cell surface receptors and cell adhesion molecules. These features have resulted in the incorporation of immunoglobulin domains into many hundreds of cell surface molecules. Recently three major advances have been made in understanding immunoglobulin receptors. One is the recognition that their intracellular binding partners are likely to link to multiple cell surface molecules, allowing cross-talk or oligomeric complex formation. A second, but related phenomenon, is their participation in cis-interactions on the extracellular surface that regulate signaling or adhesion. The third is the dramatic ability to form dozens to thousands of different isoforms via alternative splicing. Although antibodies may have been the first example of immunoglobulin-domain-containing proteins using cis-interactions to form receptor like molecules, and the grandest instance of diversity production from limited genetic material, these are clearly old ideas in this superfamily.
