Modular proteins at the cell surface

Many proteins, including cell-surface receptors, extracellular matrix (ECM) proteins and intracellular signalling systems, are constructed from a relatively small number of domains or modules. Modularity provides biological systems with a convenient way of presenting binding sites on a stable protein scaffold, in the correct position for function; it also allows regulation by module rearrangement. Knowledge about modular proteins is increasing rapidly because of good databases and more systematic approaches to protein expression and structure determination. There have been a number of important recent structures of modular proteins at the cell surface, including the low-density-lipoprotein receptor, epidermal growth factor receptor and an integrin. These and other studies show how the main task of structural biology has moved from determination of module structures to the task of assessing how modular proteins are regulated and how they bind their various ligands. These aspects are illustrated here by recent studies of modular proteins carried out in our laboratory and elsewhere. Examples will include studies of ECM proteins, such as fibronectin, and proteins associated with focal adhesion complexes that involve fibronectin, integrins and various intracellular modular proteins, such as focal adhesion kinase, Src family kinases, talin and paxillin.