LIM domains are novel sequence elements that are found in more than 60
gene products, many of which function as key regulators of developmen
tal pathways. The LIM domain, characterized by the cysteine-rich conse
nsus 2)CX(16-23)HX(2)CX(2)CX(2)CX(16-21)CX(2-3)(C/H/D), is a specific
metal-binding structure that consists of two distinct zinc-binding sub
domains. We and others have recently demonstrated that the LIM domain
mediates protein-protein interactions. However, the sequences that def
ine the protein-binding specificity of the LIM domain had not yet been
identified. Because structural studies have revealed that the C-termi
nal zinc-binding module of a LIM domain displays a tertiary fold compa
tible with nucleic acid binding, it was of interest to determine wheth
er the specific protein-binding activity of a LIM domain could be ascr
ibed to one of its two zinc-binding subdomains. To address this questi
on, we have analyzed the protein-binding capacity of a model LIM pepti
de, called zLIM1, that is derived from the cytoskeletal protein zyxin.
These studies demonstrate that the protein-binding function of zLIM1
can be mapped to sequences contained within its N-terminal zinc-bindin
g module. The C-terminal zinc-binding module of zLIM1 may thus remain
accessible to additional interactive partners. Our results raise the p
ossibility that the two structural subdomains of a LIM domain are capa
ble of performing distinct biochemical functions.