| Structural highlights
Function
LDB1_MOUSE Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions. May play a role in the development of motor neurons. Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression. Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state.[1] [2] [3] [4] [5] [6]
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 PubMed
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.
Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex.,Deane JE, Ryan DP, Sunde M, Maher MJ, Guss JM, Visvader JE, Matthews JM EMBO J. 2004 Sep 15;23(18):3589-98. Epub 2004 Sep 2. PMID:15343268[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Agulnick AD, Taira M, Breen JJ, Tanaka T, Dawid IB, Westphal H. Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Nature. 1996 Nov 21;384(6606):270-2. PMID:8918878 doi:http://dx.doi.org/10.1038/384270a0
- ↑ Jurata LW, Kenny DA, Gill GN. Nuclear LIM interactor, a rhombotin and LIM homeodomain interacting protein, is expressed early in neuronal development. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11693-8. PMID:8876198
- ↑ Bach I, Carriere C, Ostendorff HP, Andersen B, Rosenfeld MG. A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins. Genes Dev. 1997 Jun 1;11(11):1370-80. PMID:9192866
- ↑ Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH. The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13707-12. PMID:9391090
- ↑ Tran YH, Xu Z, Kato A, Mistry AC, Goya Y, Taira M, Brandt SJ, Hirose S. Spliced isoforms of LIM-domain-binding protein (CLIM/NLI/Ldb) lacking the LIM-interaction domain. J Biochem. 2006 Jul;140(1):105-19. Epub 2006 Jun 30. PMID:16815859 doi:http://dx.doi.org/10.1093/jb/mvj134
- ↑ Jurata LW, Gill GN. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol. 1997 Oct;17(10):5688-98. PMID:9315627
- ↑ Deane JE, Ryan DP, Sunde M, Maher MJ, Guss JM, Visvader JE, Matthews JM. Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex. EMBO J. 2004 Sep 15;23(18):3589-98. Epub 2004 Sep 2. PMID:15343268 doi:10.1038/sj.emboj.7600376
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