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Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis

Science, 14 September 2007
Vol. 317, Issue 5844, p. 1544-1548
DOI: 10.1126/science.1142819

Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis

  1. Eric A. Ortlund1,*,
  2. Jamie T. Bridgham2,*,
  3. Matthew R. Redinbo1,
  4. Joseph W. Thornton2,
  1. 1 Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
  2. 2 Center for Ecology and Evolutionary Biology, University of Oregon, Eugene, OR 97403, USA.
  1. To whom correspondence should be addressed. E-mail: joet{at}uoregon.edu
  • * These authors contributed equally to this work.

Abstract

The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein—the ∼450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. “Permissive” mutations—substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes—played a major role in determining GR's evolutionary trajectory.

    • Received for publication 21 March 2007.
    • Accepted for publication 6 July 2007.

    Citation:

    E. A. Ortlund, J. T. Bridgham, M. R. Redinbo, and J. W. Thornton, Crystal Structure of an Ancient Protein: Evolution by Conformational Epistasis. Science 317, 1544-1548 (2007).

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    Mol Biol Evol 32, 287-298 (1 February 2015)

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    Mol Biol Evol 32, 440-455 (1 February 2015)

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    Mol Biol Evol 32, 13-22 (1 January 2015)

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    Physiol. Rev. 95, 297-340 (1 January 2015)

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    T. Sikosek, and H. S. Chan
    J R Soc Interface 11, 20140419-20140419 (6 November 2014)

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    J. I. Boucher, P. Cote, J. Flynn, L. Jiang, A. Laban, P. Mishra, B. P. Roscoe, and D. N. A. Bolon
    Genetics 198, 461-471 (1 October 2014)

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    A. Wagner, and W. Rosen
    J R Soc Interface 11, 20131190-20131190 (6 August 2014)

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    M. Parera, and M. A. Martinez
    Mol Biol Evol 31, 1546-1553 (1 June 2014)

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    elife 3, e04126-e04126 (1 January 2014)

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    elife 3, e02304-e02304 (1 January 2014)

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    G3 2, 1085-1093 (11 November 2013)

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    W. J. Glassford, and M. Rebeiz
    Phil Trans R Soc B 368, 20130026-20130026 (11 November 2013)

    Accounting for epistatic interactions improves the functional analysis of protein structures
    A. D. Wilkins, E. Venner, D. C. Marciano, S. Erdin, B. Atri, R. C. Lua, and O. Lichtarge
    Bioinformatics 29, 2714-2721 (1 November 2013)

    Divergent Sequence Tunes Ligand Sensitivity in Phospholipid-regulated Hormone Receptors
    P. M. Musille, M. Pathak, J. L. Lauer, P. R. Griffin, and E. A. Ortlund
    J Biol Chem 288, 20702-20712 (12 July 2013)

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    S. Akanuma, Y. Nakajima, S.-i. Yokobori, M. Kimura, N. Nemoto, T. Mase, K.-i. Miyazono, M. Tanokura, and A. Yamagishi
    Proc. Natl. Acad. Sci. USA 110, 11067-11072 (2 July 2013)

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    S. Yokoyama, Y. Nakajima, S.-i. Yokobori, M. Kimura, N. Nemoto, T. Mase, K.-i. Miyazono, M. Tanokura, and A. Yamagishi
    Mol Biol Evol 30, 1495-1499 (1 July 2013)

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    C. Natarajan, N. Inoguchi, R. E. Weber, A. Fago, H. Moriyama, and J. F. Storz
    Science 340, 1324-1327 (14 June 2013)

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    A. Toth-Petroczy, and D. S. Tawfik
    Mol Biol Evol 30, 761-771 (1 April 2013)

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    Mol Biol Evol 30, 602-612 (1 March 2013)

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    R. A. Studer, B. H. Dessailly, and C. A. Orengo
    Biochem. J. 449, 581-594 (1 February 2013)

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    B. H. Dessailly, and C. A. Orengo
    elife 2, e00631-e00631 (1 January 2013)

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    BioScience 62, 939-948 (1 November 2012)

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    H. Akashi, N. Osada, and T. Ohta
    Genetics 192, 15-31 (1 September 2012)

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    D. Emera, and G. P. Wagner
    Proc. Natl. Acad. Sci. USA 109, 11246-11251 (10 July 2012)

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    Science 336, 1667-1670 (29 June 2012)

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    J. A. Kohn, K. Deshpande, and E. A. Ortlund
    J Biol Chem 287, 16267-16275 (11 May 2012)

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    M. Lynch, K. Deshpande, and E. A. Ortlund
    Mol Biol Evol 29, 1353-1366 (1 May 2012)

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    R. Huang, F. Hippauf, D. Rohrbeck, M. Haustein, K. Wenke, J. Feike, N. Sorrelle, B. Piechulla, and T. J. Barkman
    Proc. Natl. Acad. Sci. USA 109, 2966-2971 (21 February 2012)

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    G. Faure, J. Andreani, and R. Guerois
    Nucleic Acids Res 40, D847-D856 (1 January 2012)

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    L. S. Parreiras, L. M. Kohn, and J. B. Anderson
    Eukaryot Cell 10, 1348-1356 (1 October 2011)

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    G. C. Finnigan, V. Hanson-Smith, B. D. Houser, H. J. Park, and T. H. Stevens
    Mol. Biol. Cell 22, 3176-3191 (1 September 2011)

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    C. W. O'Donnell, J. Waldispuhl, M. Lis, R. Halfmann, S. Devadas, S. Lindquist, and B. Berger
    Bioinformatics 27, i34-i42 (1 July 2011)

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    Proc. Natl. Acad. Sci. USA 108, E5-E5 (11 January 2011)

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    J Biol Chem 285, 38590-38601 (3 December 2010)

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    A. Sturm, J. E. Bron, D. M. Green, and N. R. Bury
    J Mol Endocrinol 45, 391-404 (1 December 2010)

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    V. Hanson-Smith, B. Kolaczkowski, and J. W. Thornton
    Mol Biol Evol 27, 1988-1999 (1 September 2010)

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    J. D. Bloom, L. I. Gong, and D. Baltimore
    Science 328, 1272-1275 (4 June 2010)

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    S. J. Pfaff, and R. J. Fletterick
    J Biol Chem 285, 15256-15267 (14 May 2010)

    Evolutionary Expansion and Specialization of the PDZ Domains
    O. Sakarya, C. Conaco, O. Egecioglu, S. A. Solla, T. H. Oakley, and K. S. Kosik
    Mol Biol Evol 27, 1058-1069 (1 May 2010)

    Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region
    J. da Silva, M. Coetzer, R. Nedellec, C. Pastore, and D. E. Mosier
    Genetics 185, 293-303 (1 May 2010)

    Retracing Evolution of Red Fluorescence in GFP-Like Proteins from Faviina Corals
    S. F. Field, and M. V. Matz
    Mol Biol Evol 27, 225-233 (1 February 2010)

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    M. Rebeiz, J. E. Pool, V. A. Kassner, C. F. Aquadro, and S. B. Carroll
    Science 326, 1663-1667 (18 December 2009)

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    Cold Spring Harb Symp Quant Biol 0, sqb.2009.74.023v1-sqb.2009.74.023 (20 October 2009)

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    J. Yang, and M. J Young
    J Mol Endocrinol 43, 53-64 (1 August 2009)

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    P. E. Tomatis, S. M. Fabiane, F. Simona, P. Carloni, B. J. Sutton, and A. J. Vila
    Proc. Natl. Acad. Sci. USA 105, 20605-20610 (30 December 2008)

    Structure-function relationships in the mineralocorticoid receptor
    J. B Pippal, and P. J Fuller
    J Mol Endocrinol 41, 405-413 (1 December 2008)

    A protein functional leap: how a single mutation reverses the function of the transcription regulator TetR
    M. Resch, H. Striegl, E. M. Henssler, M. Sevvana, C. Egerer-Sieber, E. Schiltz, W. Hillen, and Y. A. Muller
    Nucleic Acids Res 36, 4390-4401 (1 August 2008)

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    E. J. Reschly, N. Ai, S. Ekins, W. J. Welsh, L. R. Hagey, A. F. Hofmann, and M. D. Krasowski
    J. Lipid Res. 49, 1577-1587 (1 July 2008)

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    A. Konno, T. Ogawa, T. Shirai, and K. Muramoto
    Mol Biol Evol 24, 2504-2514 (1 November 2007)

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