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NMR Solution Structure of a ldb1-LID:Lhx3-LIM complex
Structural highlights
FunctionLHX3_MOUSE Required for the establishment of the specialized cells of the pituitary gland and the nervous system (By similarity). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with Pou1f1/Pit-1.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLIM-homeodomain (LIM-HD) transcription factors form a combinatorial 'LIM code' that contributes to the specification of cell types. In the ventral spinal cord, the binary LIM homeobox protein 3 (Lhx3)/LIM domain-binding protein 1 (Ldb1) complex specifies the formation of V2 interneurons. The additional expression of islet-1 (Isl1) in adjacent cells instead specifies the formation of motor neurons through assembly of a ternary complex in which Isl1 contacts both Lhx3 and Ldb1, displacing Lhx3 as the binding partner of Ldb1. However, little is known about how this molecular switch occurs. Here, we have identified the 30-residue Lhx3-binding domain on Isl1 (Isl1(LBD)). Although the LIM interaction domain of Ldb1 (Ldb1(LID)) and Isl1(LBD) share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1(LBD) mimics Ldb1(LID). These data provide a structural basis for the formation of cell type-specific protein-protein interactions in which unstructured linear motifs with diverse sequences compete to bind protein partners. The resulting alternate protein complexes can target different genes to regulate key biological events. Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes.,Bhati M, Lee C, Nancarrow AL, Lee M, Craig VJ, Bach I, Guss JM, Mackay JP, Matthews JM EMBO J. 2008 Jul 23;27(14):2018-29. Epub 2008 Jun 26. PMID:18583962[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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