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. 1993 Nov 15;90(22):10429–10433. doi: 10.1073/pnas.90.22.10429

Multiple oligomeric states regulate the DNA binding of helix-loop-helix peptides.

R Fairman 1, R K Beran-Steed 1, S J Anthony-Cahill 1, J D Lear 1, W F Stafford 3rd 1, W F DeGrado 1, P A Benfield 1, S L Brenner 1
PMCID: PMC47790  PMID: 8248126

Abstract

To study the protein-protein interactions that allow Id, a negative regulator of cell differentiation, to inhibit the DNA-binding activities of MyoD and E47, we have synthesized peptides corresponding to the helix-loop-helix domains of MyoD, E47, and Id. We show that Id preferentially inhibits the sequence-specific DNA-binding activity of MyoD, a muscle-specific protein, as compared to E47, a more ubiquitous protein. The Id helix-loop-helix domain itself forms stable tetramers, and its inhibitory activity arises from the formation of a heterotetrameric structure with MyoD. The formation of this higher order complex provides a general mechanism by which inhibitory proteins can generate sufficient interaction free energy to overcome the large DNA-binding free energy of dimeric DNA-binding proteins.

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Selected References

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  1. Ansevin A. T., Roark D. E., Yphantis D. A. Improved ultracentrifuge cells for high-speed sedimentation equilibrium studies with interference optics. Anal Biochem. 1970 Mar;34:237–261. doi: 10.1016/0003-2697(70)90103-x. [DOI] [PubMed] [Google Scholar]
  2. Anthony-Cahill S. J., Benfield P. A., Fairman R., Wasserman Z. R., Brenner S. L., Stafford W. F., 3rd, Altenbach C., Hubbell W. L., DeGrado W. F. Molecular characterization of helix-loop-helix peptides. Science. 1992 Feb 21;255(5047):979–983. doi: 10.1126/science.1312255. [DOI] [PubMed] [Google Scholar]
  3. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  4. Biggs J., Murphy E. V., Israel M. A. A human Id-like helix-loop-helix protein expressed during early development. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1512–1516. doi: 10.1073/pnas.89.4.1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  6. Brandts J. F., Kaplan L. J. Derivative sspectroscopy applied to tyrosyl chromophores. Studies on ribonuclease, lima bean inhibitors, insulin, and pancreatic trypsin inhibitor. Biochemistry. 1973 May 8;12(10):2011–2024. doi: 10.1021/bi00734a027. [DOI] [PubMed] [Google Scholar]
  7. Brenner S. L., Zlotnick A., Stafford W. F., 3rd RecA protein self-assembly. II. Analytical equilibrium ultracentrifugation studies of the entropy-driven self-association of RecA. J Mol Biol. 1990 Dec 20;216(4):949–964. doi: 10.1016/S0022-2836(99)80013-8. [DOI] [PubMed] [Google Scholar]
  8. Buskin J. N., Hauschka S. D. Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. Mol Cell Biol. 1989 Jun;9(6):2627–2640. doi: 10.1128/mcb.9.6.2627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Christy B. A., Sanders L. K., Lau L. F., Copeland N. G., Jenkins N. A., Nathans D. An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1815–1819. doi: 10.1073/pnas.88.5.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Davis R. L., Cheng P. F., Lassar A. B., Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. doi: 10.1016/0092-8674(90)90088-v. [DOI] [PubMed] [Google Scholar]
  11. Ellis H. M., Spann D. R., Posakony J. W. extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell. 1990 Apr 6;61(1):27–38. doi: 10.1016/0092-8674(90)90212-w. [DOI] [PubMed] [Google Scholar]
  12. Farmer K., Catala F., Wright W. E. Alternative multimeric structures affect myogenin DNA binding activity. J Biol Chem. 1992 Mar 15;267(8):5631–5636. [PubMed] [Google Scholar]
  13. Ferré-D'Amaré A. R., Prendergast G. C., Ziff E. B., Burley S. K. Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain. Nature. 1993 May 6;363(6424):38–45. doi: 10.1038/363038a0. [DOI] [PubMed] [Google Scholar]
  14. Fisher D. E., Carr C. S., Parent L. A., Sharp P. A. TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family. Genes Dev. 1991 Dec;5(12A):2342–2352. doi: 10.1101/gad.5.12a.2342. [DOI] [PubMed] [Google Scholar]
  15. Garrell J., Modolell J. The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell. 1990 Apr 6;61(1):39–48. doi: 10.1016/0092-8674(90)90213-x. [DOI] [PubMed] [Google Scholar]
  16. Halazonetis T. D., Kandil A. N. Predicted structural similarities of the DNA binding domains of c-Myc and endonuclease Eco RI. Science. 1992 Jan 24;255(5043):464–466. doi: 10.1126/science.1734524. [DOI] [PubMed] [Google Scholar]
  17. Jones N. Transcriptional regulation by dimerization: two sides to an incestuous relationship. Cell. 1990 Apr 6;61(1):9–11. doi: 10.1016/0092-8674(90)90207-u. [DOI] [PubMed] [Google Scholar]
  18. Knott G. D. Mlab--a mathematical modeling tool. Comput Programs Biomed. 1979 Dec;10(3):271–280. doi: 10.1016/0010-468x(79)90075-8. [DOI] [PubMed] [Google Scholar]
  19. Lamb P., McKnight S. L. Diversity and specificity in transcriptional regulation: the benefits of heterotypic dimerization. Trends Biochem Sci. 1991 Nov;16(11):417–422. doi: 10.1016/0968-0004(91)90167-t. [DOI] [PubMed] [Google Scholar]
  20. Lassar A. B., Davis R. L., Wright W. E., Kadesch T., Murre C., Voronova A., Baltimore D., Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. doi: 10.1016/0092-8674(91)90620-e. [DOI] [PubMed] [Google Scholar]
  21. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  22. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  23. O'Shea E. K., Rutkowski R., Stafford W. F., 3rd, Kim P. S. Preferential heterodimer formation by isolated leucine zippers from fos and jun. Science. 1989 Aug 11;245(4918):646–648. doi: 10.1126/science.2503872. [DOI] [PubMed] [Google Scholar]
  24. Peterson C. A. MyoD and more. Gene Expression in Neuromuscular Development: a Keystone Symposium, Keystone, CO, USA, January 24-30, 1991. New Biol. 1991 May;3(5):442–445. [PubMed] [Google Scholar]
  25. Starovasnik M. A., Blackwell T. K., Laue T. M., Weintraub H., Klevit R. E. Folding topology of the disulfide-bonded dimeric DNA-binding domain of the myogenic determination factor MyoD. Biochemistry. 1992 Oct 20;31(41):9891–9903. doi: 10.1021/bi00156a006. [DOI] [PubMed] [Google Scholar]
  26. Sun X. H., Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell. 1991 Jan 25;64(2):459–470. doi: 10.1016/0092-8674(91)90653-g. [DOI] [PubMed] [Google Scholar]
  27. Sun X. H., Copeland N. G., Jenkins N. A., Baltimore D. Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol Cell Biol. 1991 Nov;11(11):5603–5611. doi: 10.1128/mcb.11.11.5603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vinson C. R., Garcia K. C. Molecular model for DNA recognition by the family of basic-helix-loop-helix-zipper proteins. New Biol. 1992 Apr;4(4):396–403. [PubMed] [Google Scholar]
  29. Wong I., Chao K. L., Bujalowski W., Lohman T. M. DNA-induced dimerization of the Escherichia coli rep helicase. Allosteric effects of single-stranded and duplex DNA. J Biol Chem. 1992 Apr 15;267(11):7596–7610. [PubMed] [Google Scholar]

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