THE LIM DOMAIN IS A MODULAR PROTEIN-BINDING INTERFACE

LIM domains are zinc-binding protein sequences that are found in a growing number of proteins, including certain transcriptional regulators, proto-oncogene products, and adhesion plaque constituents. Here we define the biological activity of the LIM domain through studies of an adhesion plaque protein called zyxin that displays three C-terminal LIM domains. We have used our ability to reconstitute complexes between zyxin and its two known binding partners, alpha-actinin and the cysteine-rich protein (CRP), to examine the involvement of LIM domains in protein-protein interactions. We have determined that one of the three LIM domains of zyxin is necessary and sufficient to support the association of zyxin with CRP. Our findings demonstrate that the LIM domain functions as a specific protein-binding interface.