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Protein stability promotes evolvability Jesse D. Bloom*

Summary: Protein stability promotes evolvability
Jesse D. Bloom*
, Sy T. Labthavikul*, Christopher R. Otey
, and Frances H. Arnold*
*Division of Chemistry and Chemical Engineering, Biochemistry and Molecular Biophysics Option, Mail Code 210-41, California Institute of Technology,
Pasadena, CA 91125
Edited by Michael Levitt, Stanford University School of Medicine, Stanford, CA, and approved February 14, 2006 (received for review November 21, 2005)
The biophysical properties that enable proteins to so readily evolve
to perform diverse biochemical tasks are largely unknown. Here,
we show that a protein's capacity to evolve is enhanced by the
mutational robustness conferred by extra stability. We use simu-
lations with model lattice proteins to demonstrate how extra
stability increases evolvability by allowing a protein to accept a
wider range of beneficial mutations while still folding to its native
structure. We confirm this view experimentally by mutating mar-
ginally stable and thermostable variants of cytochrome P450 BM3.
Mutants of the stabilized parent were more likely to exhibit new
or improved functions. Only the stabilized P450 parent could
tolerate the highly destabilizing mutations needed to confer novel
activities such as hydroxylating the antiinflammatory drug


Source: Arnold, Frances H. - Division of Chemistry and Chemical Engineering, California Institute of Technology
Azevedo, Ricardo - Department of Biology and Biochemistry, University of Houston


Collections: Biology and Medicine; Chemistry; Environmental Sciences and Ecology