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Acceleration of the refolding of Arc repressor by nucleic acids and other polyanions

Nature Structural Biology volume 6, pages 569–573 (1999)Cite this article

Abstract

The refolding rate of the Arc repressor dimer can be accelerated 30-fold or more by negatively charged polymers including single-stranded and double-stranded DNA, RNA, and polyvinylsulfate but not by neutral or positively charged polymers. The salt-dependence of the polyanion-mediated process and mutant studies indicate that electrostatic interactions are important in the rate acceleration. Urea-dependence studies suggest that Arc is relatively unstructured in the transition state for polyanion-stimulated refolding. At low ionic strength, the observed kinetics of refolding are consistent with a model in which denatured Arc monomers bind rapidly and nonspecifically to the polyanion and complete folding in the bound state.

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Figure 1: DNA accelerates the refolding of Arc.
Figure 2: Rate dependence on salt, PVS, and DNA concentration.
Figure 3: Urea and viscosity dependence.
Figure 4: Possible pathways for Arc refolding in the presence of polyanions (P).

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References

  1. Raumann, B.E., Brown, B.M. & Sauer, R.T. Curr. Opin. Struct. Biol. 4, 36–43 (1994).

    Article  CAS  Google Scholar 

  2. Breg, J.N., van Opheusden, J.H.J., Burgering, M.J., Boelens, R. & Kaptein, R. Nature 346, 586–589 (1990).

    Article  CAS  Google Scholar 

  3. Bonvin, A.M. et al. J. Mol. Biol. 236, 328–341 (1994).

    Article  CAS  Google Scholar 

  4. Raumann, B.E., Rould, M.A., Pabo, C.O., & Sauer, R.T. Nature 367, 75–757 (1994).

    Article  Google Scholar 

  5. Bowie, J.U. & Sauer, R.T. Biochemistry 28, 7139–7143 (1989).

    Article  CAS  Google Scholar 

  6. Milla, M.E. & Sauer, R.T. Biochemistry 33, 1125–1133 (1994).

    Article  CAS  Google Scholar 

  7. Jonsson, T., Waldburger, C.D. & Sauer, R.T. Biochemistry, 35, 4795–4802 (1996).

    Article  CAS  Google Scholar 

  8. Waldburger, C.D., Jonsson, T. & Sauer, R.T. Proc. Natl. Acad. Sci. USA 93, 2629–2634 (1996).

    Article  CAS  Google Scholar 

  9. Robinson, C.R. & Sauer, R.T. Biochemistry 35, 13878–13884 (1996).

    Article  CAS  Google Scholar 

  10. Tanford, C. Adv. Prot. Chem. 24, 1–95 (1970).

    CAS  Google Scholar 

  11. Becktel, W.J. & Schellman, J.A. Biolpolymers 26, 1859–1877 (1987).

    Article  CAS  Google Scholar 

  12. Matouschek, A. & Fersht, A.R. Proc. Natl. Acad. Sci., USA 90, 7814–7818 (1993).

    Article  CAS  Google Scholar 

  13. Milla, M.E., Brown, B.M., Waldburger, C.D. & Sauer, R.T. Biochemistry 34, 13914–13919 (1995).

    Article  CAS  Google Scholar 

  14. Neidhardt, F.C., Ingraham, J.L. & Schaechter, M. Physiology of the bacterial cell: A molecular approach. (Sinauer Associates, Sunderland, Massachusetts; 1990).

  15. Gittleman, M.S. & Matthews, C.R. Biochemistry 29, 7011–7020 (1990).

    Article  Google Scholar 

  16. Weiss, M.A. Biochemistry 29, 8020–8024 (1990).

    Article  CAS  Google Scholar 

  17. Rose, J. & Yanofsky, C. Proc. Natl. Acad. Sci. USA 71, 3134–3138 (1974).

    Article  CAS  Google Scholar 

  18. Metallo, S.J. & Schepartz, A. Nature Struct. Biol. 4, 115–117 (1997).

    Article  CAS  Google Scholar 

  19. Milla, M.E., Brown, B.M., & Sauer, R.T. Prot. Sci. 2, 2198–2205 (1993).

    Article  CAS  Google Scholar 

  20. Milla, M.E., Brown, B.M., & Sauer, R.T. Nature Struct. Biol. 1, 518–523 (1994).

    Article  CAS  Google Scholar 

  21. Brown, B.M., Milla, M.E., Smith, T.L. & Sauer, R.T. Nature Struct. Biol. 1, 164–168 (1994).

    Article  CAS  Google Scholar 

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Acknowledgements

D.R. and T.J. contributed equally to this work. Supported by NIH grants and a postdoctoral grant from the Damon Runyon/Walter Winchell Cancer Fund (D.R.). We thank B. Brown, M. Milla, and C. Robinson for mutant proteins, and F. Solomon for helpful discussions and comments on the manuscript.

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  1. Dionisios Rentzeperis

    Present address: 3D Pharmaceuticals, Exton, Pennsylvania, USA

  2. Thorlakur Jonsson

    Present address: DeCode Genetics, Reykjavik, Iceland

Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139-4703, Massachusetts, USA

    Dionisios Rentzeperis, Thorlakur Jonsson & Robert T. Sauer

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  1. Dionisios Rentzeperis
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Correspondence to Robert T. Sauer.

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Rentzeperis, D., Jonsson, T. & Sauer, R. Acceleration of the refolding of Arc repressor by nucleic acids and other polyanions. Nat Struct Mol Biol 6, 569–573 (1999). https://doi.org/10.1038/9353

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