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LIM Domain and Its Binding to Target Proteins

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Zinc Finger Proteins

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

Abstract

LIM domain is a unique double-zinc finger motif found in a variety of proteins such as homeodomain transcription factors, kinases, and adaptors. The LIM-containing proteins are involved in diverse biological processes including cytoskeleton organization, cell lineage specification and organ development. Dysfunctions of LIM domains induce pathological effects including muscle detachment, embryonic lethality, and oncogenesis. Acting as a protein-protein interaction motif, the LIM domain has a conserved scaffold but highly variable mode in recognizing diverse target proteins. This chapter describes the structure and function of LIM domain proteins and discusses the molecular basis by which the domain mediates protein-protein interactions.

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References

  1. Karlsson O, Thor S, Norberg T et al. Insulin gene enhancer binding protein Isl-1 is a member of a novel class of proteins containing both a homeo-and a Cys-His domain. Nature 1990; 344:879–882.

    Article  PubMed  CAS  Google Scholar 

  2. Freyd G, Kim SK, Horvitz HR. Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature 1990; 344:876–879.

    Article  PubMed  CAS  Google Scholar 

  3. Taira M, Evrard JL, Steinmetz A et al. Classification of LIM proteins. Trends Genet 1995; 11:431–432.

    Article  PubMed  CAS  Google Scholar 

  4. Dawid IB, Toyama R, Taira M. LIM domain proteins. CR Acad Sci III 1995; 318:295–306.

    CAS  Google Scholar 

  5. Dawid IB, Breen JJ, Toyama R. LIM domains: Multiple roles as adapters and functional modifiers in protein interactions. Trends Genet 1998; 14:156–162.

    Article  PubMed  CAS  Google Scholar 

  6. Hobert O and Westphal H. Functions of LIM-homeobox genes. Trends Genet 2000; 16:75–83.

    Article  PubMed  CAS  Google Scholar 

  7. Rabbitts, T.H. LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes. Genes Dev 1998; 12(17):2651–7

    PubMed  CAS  Google Scholar 

  8. Larson RC, Osada H, Larson TA et al. The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 1995; 11(5):853–62

    PubMed  CAS  Google Scholar 

  9. Larson RC, Lavenir I, Larson TA et al. Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. EMBO J 1996; 15(5):1021–7

    PubMed  CAS  Google Scholar 

  10. Bach I. The LIM domain: Regulation by association. Mech. Dev 2000; 91:5–17.

    CAS  Google Scholar 

  11. Arber S, Barbayannis FA, Hanser H et al. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase. Nature 1998; 39:805–809.

    Google Scholar 

  12. Yang, N, Higuchi, O, Ohashi, K et al. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. Nature 1998; 393:809–812.

    Article  PubMed  CAS  Google Scholar 

  13. Khurana, T, Khurana, B, Noegel, AA. LIM proteins: Association with the actin cytoskeleton. Protoplasma 2002; 219:1–12.

    Article  PubMed  CAS  Google Scholar 

  14. Arber S, Halder G, Caroni P. Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 1994; 79:221–231.

    Article  PubMed  CAS  Google Scholar 

  15. Louis HA, Pino JD, Schmeichel KL et al. Comparison of three members of the cysteine-rich protein family reveals functional conservation and divergent patterns of gene expression. J Biol Chem 1997; 272:27484–27491.

    Article  PubMed  CAS  Google Scholar 

  16. Sadler I, Crawford AW, Michelsen JW et al. Zyxin and cCRP: Two interactive LIM domain proteins associated with the cytoskeleton. J Cell Biol 1992; 119:1573–1587.

    Article  PubMed  CAS  Google Scholar 

  17. Flick MJ, Konieczny SF. The muscle regulatory and structural protein MLP is a cytoskeletal binding partner of betal-spectrin. J Cell Sci 2000; 113(Pt 9):1553–1564.

    PubMed  CAS  Google Scholar 

  18. Wu C, Dedhar S. Integrin-linked kinase (ILK) and its interactors: A new paradigm for the coupling of extracellular matrix to actin cytoskeleton and signaling complexes. J Cell Biol 2001; 155:505–510.

    Article  PubMed  CAS  Google Scholar 

  19. Wang Y, Gilmore TD. Zyxin and paxillin proteins: Focal adhesion plaque LIM domain proteins go nuclear. Biochim Biophys Acta 2003; 1593(2–3):115–20.

    PubMed  CAS  Google Scholar 

  20. Michelsen JW, Schmeichel KL, Beckerle MC et al. The LIM motif defines a specific zinc-binding protein domain. Proc Natl Acad Sci USA 1993; 90:4404–4408.

    Article  PubMed  CAS  Google Scholar 

  21. Kosa JL, Michelsen JW, Louis HA et al. Common metal ion coordination in LIM domain proteins. Biochemistry 1994; 33:468–477.

    Article  PubMed  CAS  Google Scholar 

  22. Michelsen JW, Sewell AK, Louis HA et al. Mutational analysis of the metal sites in an LIM domain. J Biol Chem 1994; 269:11108–11113.

    PubMed  CAS  Google Scholar 

  23. Velyvis A, Yang Y, Wu C et al. Solution structure of the focal adhesion adaptor PINCH LIM1 domain and characterization of its interaction with the integrin-linked kinase ankyrin repeat domain. J Biol Chem 2001; 276:4932–4939.

    Article  PubMed  CAS  Google Scholar 

  24. Velyvis A, Vaynberg J, Yang Y et al. Structural and functional insights into PINCH LIM 4 domain-mediated integrin signaling Nat Struct Biol 2003; 10:558–564.

    Article  PubMed  CAS  Google Scholar 

  25. Agulnick AD, Taira M, Breen JJ et al. Interactions of the LIM-domain-binding factor Ldb1 with LIM homeodomain proteins. Nature 1996; 384:270–272.

    Article  PubMed  CAS  Google Scholar 

  26. 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 USA 1996; 93:11693–11698.

    Article  PubMed  CAS  Google Scholar 

  27. Jurata LW, Pfaff SL, Gill GN. The nuclear LIM domain interactor NLI mediates homo-and heterodimerization of LIM domain transcription factors. J Biol Chem 1998; 273:3152–3157.

    Article  PubMed  CAS  Google Scholar 

  28. Jurata LW, Gill GN. Functional analysis of the nuclear LIM domain interactor NLI. Mol Cell Biol 1997; 17:5688–5698.

    PubMed  CAS  Google Scholar 

  29. Breen JJ, Agulnick AD, Westphal H et al. Interactions between LIM domains and the LIM domain-binding protein Ldb1. J Biol Chem 1998; 273:4712–4717.

    Article  PubMed  CAS  Google Scholar 

  30. Deane JE, Sum E, Mackay JP et al. Design, production and characterization of FLIN2 and FLIN4: The engineering of intramolecular ldb1: LMO complexes. Protein Eng 2001; 14:493–499.

    Article  PubMed  CAS  Google Scholar 

  31. Netchine I, Sobrier ML, Krude H et al. Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nat Genet 2000;25:182–186.

    Article  PubMed  CAS  Google Scholar 

  32. Howard PW, Maurer RA. A Point Mutation in the LIM Domain of Lhx3 Reduces Activation of the Glycoprotein Hormone alpha-Subunit Promoter. J Biol Chem 2001; 276:19020–19026.

    Article  PubMed  CAS  Google Scholar 

  33. Bach I, Rodriguez-Esteban C, Carriere C et al. RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex. Nat Genet 1999; 22:394–399.

    Article  PubMed  CAS  Google Scholar 

  34. Ostendorff HP, Peirano RI, Peters MA et al. Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors. Nature 2002; 416:99–103.

    Article  PubMed  CAS  Google Scholar 

  35. Crawford AW, Pino JD, Beckerle MC. Biochemical and molecular characterization of the chicken cysteine-rich protein, a developmentally regulated LIM-domain protein that is associated with the actin cytoskeleton. J Cell Biol 1994; 124:117–127.

    Article  PubMed  CAS  Google Scholar 

  36. Crawford AW, Michelsen JW, Beckerle MC. An interaction between zyxin and alpha-actinin. J Cell Biol 1992; 116:1381–1393.

    Article  PubMed  CAS  Google Scholar 

  37. Hobert O, Schilling JW, Beckerle MC et al. SH3 domain-dependent interaction of the proto-oncogene product Vav with the focal contact protein zyxin. Oncogene 1996; 12:1577–1581.

    PubMed  CAS  Google Scholar 

  38. Yi J, Kloeker S, Jensen CC et al. Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers. J Biol Chem 2002; 277:9580–9589.

    Article  PubMed  CAS  Google Scholar 

  39. Drees B, Friederich E, Fradelizi J et al. Characterization of the interaction between zyxin and members of the Ena/vasodilator-stimulated phosphoprotein family of proteins. J Biol Chem 2000; 275:22503–22511.

    Article  PubMed  CAS  Google Scholar 

  40. Schmeichel KL, Beckerle MC. The LIM domain is a modular protein-binding interface. Cell 1994; 79:211–219.

    Article  PubMed  CAS  Google Scholar 

  41. Hammarstrom A, Berndt KD, Sillard R et al. Solution structure of a naturally-occurring zinc-peptide complex demonstrates that the N-terminal zinc-binding module of the Lasp-1 LIM domain is an independent folding unit. Biochem 1996; 35:12723–12732.

    Article  CAS  Google Scholar 

  42. Schmeichel KL, Beckerle MC. Molecular dissection of a LIM domain. Mol Biol Cell 1997; 8:219–230.

    PubMed  CAS  Google Scholar 

  43. Schmeichel KL, Beckerle MC. LIM domains of cysteine-rich protein 1 (CRP1) are essential for its zyxin-binding function. Biochem J 1998; 331(Pt 3):885–892.

    PubMed  CAS  Google Scholar 

  44. Yao X, Perez-Alvarado GC, Louis HA et al. Solution structure of the chicken cysteine-rich protein, CRP1, a double-LIM protein implicated in muscle differentiation. Biochem 1999; 38:5701–5713.

    Article  CAS  Google Scholar 

  45. Nix DA, Fradelizi J, Bockholt S et al. Targeting of zyxin to sites of actin membrane interaction and to the nucleus. J Biol Chem 2001; 276:34759–34767.

    Article  PubMed  CAS  Google Scholar 

  46. Beckerle MC. Zyxin: Zinc fingers at sites of cell adhesion. Bioessays 1997; 19:949–957.

    Article  PubMed  CAS  Google Scholar 

  47. Fradelizi J, Noireaux V, Plastino J et al. ActA and human zyxin harbour Arp2/3-independent actin-polymerization activity. Nat Cell Biol 2001; 3:699–707.

    Article  PubMed  CAS  Google Scholar 

  48. Turner CE. Paxillin and focal adhesion signaling. Nat Cell Biol 2000; 2:E231–E236.

    Article  PubMed  CAS  Google Scholar 

  49. Cote JF, Turner CE, Tremblay ML. Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase-PEST. J Biol Chem 1999; 274:20550–20560.

    Article  PubMed  CAS  Google Scholar 

  50. Shen Y, Schneider G, Cloutier JF et al. Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J Biol Chem 1998; 273:6474–6481.

    Article  PubMed  CAS  Google Scholar 

  51. Cote JF, Turner CE, Tremblay ML. Intact LIM 3 and LIM 4 domains of paxillin are required for the association to a novel polyproline region (Pro 2) of protein-tyrosine phosphatase-PEST. J Biol Chem 1999; 274:20550–20560.

    Article  PubMed  CAS  Google Scholar 

  52. Shen Y, Lyons P, Cooley M et al. The noncatalytic domain of protein-tyrosine phosphatase-PEST targets paxillin for dephosphorylation in vivo. J Biol Chem 2000; 275:1405–1413.

    Article  PubMed  CAS  Google Scholar 

  53. Brown MC, Perrotta JA, Turner CE. Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding. J Cell Biol 1996; 135:1109–1123.

    Article  PubMed  CAS  Google Scholar 

  54. Herreros L, Rodriguez-Fernandez JL, Brown MC et al. Paxillin localizes to the lymphocyte microtubule organizing center and associates with the microtubule cytoskeleton. J Biol Chem 2000; 275:26436–26440.

    Article  PubMed  CAS  Google Scholar 

  55. Nishiya N, Iwabuchi Y, Shibanuma M et al. Hic-5, a Paxillin Homologue, Binds to the Protein-tyrosine Phosphatase PEST (PTP-PEST) through Its LIM 3áDomain. J Biol Chem 1999; 274:9847–9853.

    Article  PubMed  CAS  Google Scholar 

  56. Wu RY, Gill GN. LIM domain recognition of a tyrosine-containing tight turn. J Biol Chem 1994; 269:25085–25090.

    PubMed  CAS  Google Scholar 

  57. Durick K, Wu RY, Gill GN et al. Mitogenic Signaling by Ret/ptc2 Requires Association with Enigma via a LIM Domain. J Biol Chem 1996; 271:12691–12694.

    Article  PubMed  CAS  Google Scholar 

  58. Wu RY, Durick K, Songyang Z et al. Specificity of LIM Domain Interactions with Receptor Tyrosine Kinases. J Biol Chem 1996; 271:15934–15941.

    Article  PubMed  CAS  Google Scholar 

  59. Rearden A. A new LIM protein containing an autoepitope homologous to “senescent cell antigen.” Biochem Biophys Res Commun 1994; 201:1124–1131.

    Article  PubMed  CAS  Google Scholar 

  60. Tu Y, Li F, Goicoechea S et al. The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. Mol Cell Biol 1999; 19:2425–2434.

    PubMed  CAS  Google Scholar 

  61. Li F, Zhang Y, Wu C. Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats. J Cell Sci 1999; 112(Pt 24):4589–4599.

    PubMed  CAS  Google Scholar 

  62. Tu Y, Li F, Wu C. Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways. Mol Biol Cell 1998; 9:3367–3382.

    PubMed  CAS  Google Scholar 

  63. Perez-Alvarado GC, Miles C, Michelsen JW et al. Structure of the carboxy-terminal LIM domain from the cysteine rich protein CRP. Nat Struct Biol 1994; 1:388–398.

    Article  PubMed  CAS  Google Scholar 

  64. Deane JE, Mackay JP, Kwan AH et al. Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4. EMBO J 2003, 22(9):2224–33

    Article  PubMed  CAS  Google Scholar 

  65. Perez-Alvarado GC, Kosa JL, Louis HA et al. Structure of the cysteine-rich intestinal protein, CRIP. J Mol Biol 1996; 257:153–174.

    Article  PubMed  CAS  Google Scholar 

  66. Konrat R, Weiskirchen R, Krautler B et al. Solution structure of the carboxyl-terminal LIM domain from quail cysteine-rich protein CRP2. J Biol Chem 1997; 272:12001–12007.

    Article  PubMed  CAS  Google Scholar 

  67. Kontaxis G, Konrat R, Krautler B et al. Structure and intramodular dynamics of the amino-terminal LIM domain from quail cysteine-and glycine-rich protein CRP2. Biochem 1998; 37:7127–7134.

    Article  CAS  Google Scholar 

  68. Li SC, Zwahlen C, Vincent SJ et al. Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity. Nat Struct Biol 1998; 5:1075–83.

    Article  PubMed  CAS  Google Scholar 

  69. Mallis RJ, Brazin KN, Fulton DB et al. Structural characterization of a proline-driven conformational switch within the Itk SH2 domain. Nat Struct Biol 2002; 9:900–5.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmacology School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

    Algirdas Velyvis

  2. Structural Biology Program The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA

    Jun Qin

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  1. Algirdas Velyvis
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  2. Jun Qin
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Correspondence to Jun Qin .

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Editors and Affiliations

  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

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© 2005 Landes Bioscience/Eurekah.com and Kluwer Academic/Plenum Publishers

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Velyvis, A., Qin, J. (2005). LIM Domain and Its Binding to Target Proteins. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_15

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