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Implementing the LIM code: the structural basis for cell type‐specific assembly of LIM‐homeodomain complexes
Author(s) -
Bhati Mugdha,
Lee Christopher,
Nancarrow Amy L,
Lee Mihwa,
Craig Vanessa J,
Bach Ingolf,
Guss J Mitchell,
Mackay Joel P,
Matthews Jacqueline M
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.123
Subject(s) - biology , library science , art history , history , computer science
LIM‐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.