Abstract
Borrowing concepts from the schema theory of genetic algorithms, we have developed a computational algorithm to identify the fragments of proteins, or schemas, that can be recombined without disturbing the integrity of the three-dimensional structure. When recombination leaves these schemas undisturbed, the hybrid proteins are more likely to be folded and functional. Crossovers found by screening libraries of several randomly shuffled proteins for functional hybrids strongly correlate with those predicted by this approach. Experimental results from the construction of hybrids of two β-lactamases that share 40% amino acid identity demonstrate a threshold in the amount of schema disruption that the hybrid protein can tolerate. To the extent that introns function to promote recombination within proteins, natural selection would serve to bias their locations to schema boundaries.
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Change history
10 June 2002
Updated PDF, image updated
Notes
*Note: A mistake was introduced during the production process of this paper. In the AOP version of the paper, footnote 6 of Table 1 was mistakenly placed after the MIC value of hybrid 2A. The correct position for footnote 6 should be after the MIC value of hybrid 1A; 2,5606 . This mistake has been corrected in the HTML version and will appear correctly in print. The PDF version available online has been appended.
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Acknowledgements
C.A.V. is supported by a National Science Foundation graduate research fellowship and the California Institute of Technology Initiative in Computational Molecular Biology, a Burroughs Wellcome funded program for science at the interface. Z.G.W. acknowledges the support by the W.M. Keck Foundation. S.L.M. is supported by the Howard Hughes Medical Institute, the Ralph M. Parsons Foundation and an IBM Shared University Research Grant. The PSE-4 gene and the PMON vector were provided by R.C. Levesque (Université Laval, Québec, Canada).
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Voigt, C., Martinez, C., Wang, ZG. et al. Protein building blocks preserved by recombination. Nat Struct Mol Biol 9, 553–558 (2002). https://doi.org/10.1038/nsb805
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DOI: https://doi.org/10.1038/nsb805
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