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Publication Abstract from PubMed

of LIM-homeodomain proteins form a transcriptional 'LIM code' to direct the specification of neural cell types. Two paralogous pairs of LIM-homeodomain proteins, LIM homeobox protein 3/4 (Lhx3/Lhx4) and Islet-1/2 (Isl1/Isl2) are expressed in developing ventral motor neurons. Lhx3 and Isl1 interact within a well-characterised transcriptional complex that triggers motor neuron development, but it was not known if Lhx4 and Isl2 could participate in equivalent complexes. We have identified an Lhx3-binding domain (LBD) in Isl2 based on sequence homology with the Isl1(LBD) and show that both Isl2(LBD) and Isl1(LBD) can bind each of Lhx3 and Lhx4. X-ray crystal and SAXS-derived solution structures of an Lhx4:Isl2 complex exhibit many similarities with that of Lhx3:Isl1; however, structural differences supported by mutagenic studies reveal differences in the mechanisms of binding. Differences in binding have implications for the mode of exchange of protein partners in transcriptional complexes, and indicate a divergence in functions of Lhx3/4 and Isl1/2. The formation of weaker Lhx:Isl complexes would likely be masked by the availability of the other Lhx:Isl complexes in post mitotic motor neurons.

The structural basis for partial redundancy in a class of transcription factors, the lim-homeodomain proteins, in neural cell type specification.,Gadd MS, Bhati M, Jeffries CM, Langley DB, Trewhella J, Guss JM, Matthews JM J Biol Chem. 2011 Oct 24. PMID:22025611^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.