Tandem LIM domains provide synergistic binding in the LMO4 : Ldb1 complex
- Author(s)
- Deane, JE; Ryan, DP; Sunde, M; Maher, MJ; Guss, JM; Visvader, JE; Matthews, JM;
- Details
- Publication Year 2004-09-15,Volume 23,Issue #18,Page 3589-3598
- Journal Title
- EMBO JOURNAL
- Publication Type
- Journal Article
- 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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- CELL ACUTE-LEUKEMIA; PROTEIN LMO2; ONLY PROTEIN; MACROMOLECULAR STRUCTURES; TRANSCRIPTION FACTORS; HOMEODOMAIN ACTIVITY; INTERACTOR NLI; HOMEOBOX GENE; LDB1; MICE
- Publisher's Version
- https://doi.org/10.1038/sj.emboj.7600376
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-09-15 12:00:00