2jtn › Citations

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 27 2018-29 (2008)
Cited: 51 times
EuropePMC logo PMID: 18583962

Abstract

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.

Reviews - 2jtn mentioned but not cited (1)

  1. Linkers in the structural biology of protein-protein interactions. Reddy Chichili VP, Kumar V, Sivaraman J. Protein Sci 22 153-167 (2013)

Articles - 2jtn mentioned but not cited (7)

  1. 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 27 2018-2029 (2008)
  2. A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. Gadd MS, Jacques DA, Nisevic I, Craig VJ, Kwan AH, Guss JM, Matthews JM. J Biol Chem 288 21924-21935 (2013)
  3. Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss. Ramzan K, Bin-Abbas B, Al-Jomaa L, Allam R, Al-Owain M, Imtiaz F. BMC Endocr Disord 17 17 (2017)
  4. Solution structure of the LIM-homeodomain transcription factor complex Lhx3/Ldb1 and the effects of a pituitary mutation on key Lhx3 interactions. Bhati M, Lee C, Gadd MS, Jeffries CM, Kwan A, Whitten AE, Trewhella J, Mackay JP, Matthews JM. PLoS One 7 e40719 (2012)
  5. Solution structure of a tethered Lmo2(LIM2) /Ldb1(LID) complex. Dastmalchi S, Wilkinson-White L, Kwan AH, Gamsjaeger R, Mackay JP, Matthews JM. Protein Sci 21 1768-1774 (2012)
  6. Crystallization and diffraction of an Lhx4-Isl2 complex. Gadd MS, Langley DB, Guss JM, Matthews JM. Acta Crystallogr Sect F Struct Biol Cryst Commun 65 151-153 (2009)
  7. Crystallization and diffraction of an Isl1-Ldb1 complex. Gadd MS, Jacques DA, Guss JM, Matthews JM. Acta Crystallogr Sect F Struct Biol Cryst Commun 68 1398-1401 (2012)


Reviews citing this publication (5)

  1. Macromolecular NMR spectroscopy for the non-spectroscopist. Kwan AH, Mobli M, Gooley PR, King GF, Mackay JP. FEBS J 278 687-703 (2011)
  2. Generating spinal motor neuron diversity: a long quest for neuronal identity. Francius C, Clotman F. Cell Mol Life Sci 71 813-829 (2014)
  3. Expression and function of the LIM-homeodomain transcription factor Islet-1 in the developing and mature vertebrate retina. Bejarano-Escobar R, Álvarez-Hernán G, Morona R, González A, Martín-Partido G, Francisco-Morcillo J. Exp Eye Res 138 22-31 (2015)
  4. The tandem β-zipper: modular binding of tandem domains and linear motifs. Matthews JM, Potts JR. FEBS Lett 587 1164-1171 (2013)
  5. Molecular Aspects of the Development and Function of Auditory Neurons. Pavlinkova G. Int J Mol Sci 22 E131 (2020)

Articles citing this publication (38)

  1. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Nedelsky NB, Pennuto M, Smith RB, Palazzolo I, Moore J, Nie Z, Neale G, Taylor JP. Neuron 67 936-952 (2010)
  2. Lmx1a is required for segregation of sensory epithelia and normal ear histogenesis and morphogenesis. Nichols DH, Pauley S, Jahan I, Beisel KW, Millen KJ, Fritzsch B. Cell Tissue Res 334 339-358 (2008)
  3. Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex. El Omari K, Hoosdally SJ, Tuladhar K, Karia D, Vyas P, Patient R, Porcher C, Mancini EJ. Blood 117 2146-2156 (2011)
  4. Islet-1 Is essential for pancreatic β-cell function. Ediger BN, Du A, Liu J, Hunter CS, Walp ER, Schug J, Kaestner KH, Stein R, Stoffers DA, May CL. Diabetes 63 4206-4217 (2014)
  5. Lmo4 and Clim1 progressively delineate cortical projection neuron subtypes during development. Azim E, Shnider SJ, Cederquist GY, Sohur US, Macklis JD. Cereb Cortex 19 Suppl 1 i62-9 (2009)
  6. The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2. Zhang H, Wang WP, Guo T, Yang JC, Chen P, Ma KT, Guan YF, Zhou CY. J Mol Biol 392 566-577 (2009)
  7. LIM domain binding proteins 1 and 2 have different oligomeric states. Cross AJ, Jeffries CM, Trewhella J, Matthews JM. J Mol Biol 399 133-144 (2010)
  8. 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 286 42971-42980 (2011)
  9. Expression of LIM-homeodomain transcription factors in the developing and mature mouse retina. Balasubramanian R, Bui A, Ding Q, Gan L. Gene Expr Patterns 14 1-8 (2014)
  10. Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification. Simmons DK, Pang K, Martindale MQ. Evodevo 3 2 (2012)
  11. Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A. Boëda B, Knowles PP, Briggs DC, Murray-Rust J, Soriano E, Garvalov BK, McDonald NQ, Way M. J Biol Chem 286 11543-11554 (2011)
  12. The LIM homeodomain transcription factor LHX6: a transcriptional repressor that interacts with pituitary homeobox 2 (PITX2) to regulate odontogenesis. Zhang Z, Gutierrez D, Li X, Bidlack F, Cao H, Wang J, Andrade K, Margolis HC, Amendt BA. J Biol Chem 288 2485-2500 (2013)
  13. Chondrolectin mediates growth cone interactions of motor axons with an intermediate target. Zhong Z, Ohnmacht J, Reimer MM, Bach I, Becker T, Becker CG. J Neurosci 32 4426-4439 (2012)
  14. Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4. Cubeddu L, Joseph S, Richard DJ, Matthews JM. PLoS One 7 e39218 (2012)
  15. Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice. Chumak T, Bohuslavova R, Macova I, Dodd N, Buckiova D, Fritzsch B, Syka J, Pavlinkova G. Mol Neurobiol 53 2368-2383 (2016)
  16. Biophysical properties of intrinsically disordered p130Cas substrate domain--implication in mechanosensing. Hotta K, Ranganathan S, Liu R, Wu F, Machiyama H, Gao R, Hirata H, Soni N, Ohe T, Hogue CW, Madhusudhan MS, Sawada Y. PLoS Comput Biol 10 e1003532 (2014)
  17. Symptomatic heterozygotes and prenatal diagnoses in a nonconsanguineous family with syndromic combined pituitary hormone deficiency resulting from two novel LHX3 mutations. Sobrier ML, Brachet C, Vié-Luton MP, Perez C, Copin B, Legendre M, Heinrichs C, Amselem S. J Clin Endocrinol Metab 97 E503-9 (2012)
  18. The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating Transcriptional Pathways that Enhance Its Own Expression and Formation. Erb M, Lee B, Yeon Seo S, Lee JW, Lee S, Lee SK. eNeuro 4 ENEURO.0349-16.2017 (2017)
  19. The stage-dependent roles of Ldb1 and functional redundancy with Ldb2 in mammalian retinogenesis. Gueta K, David A, Cohen T, Menuchin-Lasowski Y, Nobel H, Narkis G, Li L, Love P, de Melo J, Blackshaw S, Westphal H, Ashery-Padan R. Development 143 4182-4192 (2016)
  20. LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis. Wu Y, Luo H, Liu J, Kang D, McNeilly AS, Cui S. Endocrinology 151 4787-4800 (2010)
  21. The islet-expressed Lhx1 transcription factor interacts with Islet-1 and contributes to glucose homeostasis. Bethea M, Liu Y, Wade AK, Mullen R, Gupta R, Gelfanov V, DiMarchi R, Bhatnagar S, Behringer R, Habegger KM, Hunter CS. Am J Physiol Endocrinol Metab 316 E397-E409 (2019)
  22. A variant in LMX1A causes autosomal recessive severe-to-profound hearing impairment. Schrauwen I, Chakchouk I, Liaqat K, Jan A, Nasir A, Hussain S, Nickerson DA, Bamshad MJ, Ullah A, Ahmad W, Leal SM. Hum Genet 137 471-478 (2018)
  23. Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins. Siddiqui MQ, Badmalia MD, Patel TR. Int J Mol Sci 22 2647 (2021)
  24. The role of Islet-1 in cell specification, differentiation, and maintenance of phenotypes in the vertebrate neural retina. Martín-Partido G, Francisco-Morcillo J. Neural Regen Res 10 1951-1952 (2015)
  25. The structure of an LIM-only protein 4 (LMO4) and Deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4. Joseph S, Kwan AH, Stokes PH, Mackay JP, Cubeddu L, Matthews JM. PLoS One 9 e109108 (2014)
  26. Structural basis of the interaction of the breast cancer oncogene LMO4 with the tumour suppressor CtIP/RBBP8. Stokes PH, Liew CW, Kwan AH, Foo P, Barker HE, Djamirze A, O'Reilly V, Visvader JE, Mackay JP, Matthews JM. J Mol Biol 425 1101-1110 (2013)
  27. A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis. Jing Y, Ren Y, Witzel HR, Dobreva G. Stem Cell Reports 16 1894-1905 (2021)
  28. Alternative splicing of the LIM-homeodomain transcription factor Isl1 in the mouse retina. Whitney IE, Kautzman AG, Reese BE. Mol Cell Neurosci 65 102-113 (2015)
  29. Disparate binding kinetics by an intrinsically disordered domain enables temporal regulation of transcriptional complex formation. Robertson NO, Smith NC, Manakas A, Mahjoub M, McDonald G, Kwan AH, Matthews JM. Proc Natl Acad Sci U S A 115 4643-4648 (2018)
  30. Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1. Yan C, Yu C, Zhang D, Cui Y, Zhou J, Cui S. Sci Rep 6 39308 (2016)
  31. Critical Role of LMCD1 in Promoting Profibrotic Characteristics of Lung Myofibroblasts in Experimental and Scleroderma-Associated Lung Fibrosis. Bogatkevich GS, Atanelishvili I, Bogatkevich AM, Silver RM. Arthritis Rheumatol 75 438-448 (2023)
  32. Cysteine 397 plays important roles in the folding of the neuron-restricted silencer factor/RE1-silencing transcription factor. Zhang Y, Hu W, Shen J, Tong X, Yang Z, Shen Z, Lan W, Wu H, Cao C. Biochem Biophys Res Commun 414 309-314 (2011)
  33. Genes expressed in mouse cortical progenitors are enriched in Pax, Lhx, and Sox transcription factor putative binding sites. Bery A, Mérot Y, Rétaux S. Brain Res 1633 37-51 (2016)
  34. Hearing impairment locus heterogeneity and identification of PLS1 as a new autosomal dominant gene in Hungarian Roma. Schrauwen I, Melegh BI, Chakchouk I, Acharya A, Nasir A, Poston A, Cornejo-Sanchez DM, Szabo Z, Karosi T, Bene J, Melegh B, Leal SM. Eur J Hum Genet 27 869-878 (2019)
  35. Interactions between LHX3- and ISL1-family LIM-homeodomain transcription factors are conserved in Caenorhabditis elegans. Bhati M, Llamosas E, Jacques DA, Jeffries CM, Dastmalchi S, Ripin N, Nicholas HR, Matthews JM. Sci Rep 7 4579 (2017)
  36. A Quantitative Fluorescence-Based Assay for Assessing LIM Domain-Peptide Interactions. Robertson NO, Shah M, Matthews JM. Angew Chem Int Ed Engl 55 13236-13239 (2016)
  37. Contrasting DNA-binding behaviour by ISL1 and LHX3 underpins differential gene targeting in neuronal cell specification. Smith NC, Wilkinson-White LE, Kwan AHY, Trewhella J, Matthews JM. J Struct Biol X 5 100043 (2021)
  38. Mutation in a flexible linker modulates binding affinity for modular complexes. Stokes PH, Robertson NO, Silva APG, Estephan T, Trewhella J, Guss JM, Matthews JM. Proteins 87 425-429 (2019)


Quick links