Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes

Journal Article · Wed Sep 03 04:00:00 EDT 2008 · EMBO J.

DOI:https://doi.org/10.1038/emboj.2008.123· OSTI ID:1006779

Bhati, Mugdha; Lee, Christopher; Nancarrow, Amy L; Lee, Mihwa; Craig, Vanessa J; Bach, Ingolf; Guss, J Mitchell; Mackay, Joel P; Matthews, Jacqueline M ^[1]

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1. UMASS, MED

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{sub LBD}). Although the LIM interaction domain of Ldb1 (Ldb1{sub LID}) and Isl1{sub LBD} share low levels of sequence homology, X-ray and NMR structures reveal that they bind Lhx3 in an identical manner, that is, Isl1{sub LBD} mimics Ldb1{sub 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006779
• Journal Information: EMBO J., Journal Name: EMBO J. Journal Issue: 2008 Vol. 27; ISSN EMJODG; ISSN 0261-4189
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
GENES
MOTORS
NERVE CELLS
PROTEINS
SPECIFICATIONS
SPINAL CORD
TARGETS
TRANSCRIPTION FACTORS