The structure of an LIM-only protein 4 (LMO4) and Deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4.

The structure of an LIM-only protein 4 (LMO4) and Deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4.

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LIM-domain only protein 4 (LMO4) is a widely expressed protein with important roles in embryonic development and breast cancer.It has been reported to bind many partners, including the transcription factor helo baby salve Deformed epidermal autoregulatory factor-1 (DEAF1), with which LMO4 shares many biological parallels.We used yeast two-hybrid assays to show that DEAF1 binds both LIM domains of LMO4 and that DEAF1 binds the same face on LMO4 as two other LMO4-binding partners, namely LIM domain binding protein 1 (LDB1) and C-terminal binding protein interacting protein (CtIP/RBBP8).Mutagenic screening analysed by the same method, indicates that the key residues in the interaction lie in modbiv LMO4LIM2 and the N-terminal half of the LMO4-binding domain in DEAF1.We generated a stable LMO4LIM2-DEAF1 complex and determined the solution structure of that complex.

Although the LMO4-binding domain from DEAF1 is intrinsically disordered, it becomes structured on binding.The structure confirms that LDB1, CtIP and DEAF1 all bind to the same face on LMO4.LMO4 appears to form a hub in protein-protein interaction networks, linking numerous pathways within cells.Competitive binding for LMO4 therefore most likely provides a level of regulation between those different pathways.