Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex
Open Access
- 2 September 2004
- journal article
- Published by Springer Nature in The EMBO Journal
- Vol. 23 (18) , 3589-3598
- https://doi.org/10.1038/sj.emboj.7600376
Abstract
Nuclear LIM‐only (LMO) and LIM‐homeodomain (LIM‐HD) proteins have important roles in cell fate determination, organ development and oncogenesis. These proteins contain tandemly arrayed LIM domains that bind the LIM interaction domain (LID) of the nuclear adaptor protein LIM domain‐binding protein‐1 (Ldb1). We have determined a high‐resolution X‐ray crystal structure of LMO4, a putative breast oncoprotein, in complex with Ldb1‐LID, providing the first example of a tandem LIM:Ldb1‐LID complex and the first structure of a type‐B LIM domain. The complex possesses a highly modular structure with Ldb1‐LID binding in an extended manner across both LIM domains of LMO4. The interface contains extensive hydrophobic and electrostatic interactions and multiple backbone–backbone hydrogen bonds. A mutagenic screen of Ldb1‐LID, assessed by yeast two‐hybrid and competition ELISA analysis, identified key features at the interface and revealed that the interaction is tolerant to mutation. These combined properties provide a mechanism for the binding of Ldb1 to numerous LMO and LIM‐HD proteins. Furthermore, the modular extended interface may form a general mode of binding to tandem LIM domains.Keywords
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