Protein stability promotes evolvability

by: Jesse D Bloom, Sy T Labthavikul, Christopher R Otey, Frances H Arnold

PNAS, Vol. 103, No. 15. (11 April 2006), pp. 5869-5874.

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摘要

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 simulations 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 marginally 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 naproxen. Our work establishes a crucial link between protein stability and evolution. We show that we can exploit this link to discover protein functions, and we suggest how natural evolution might do the same. 10.1073/pnas.0510098103

@article{citeulike:582306, abstract = {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 simulations 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 marginally 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 naproxen. Our work establishes a crucial link between protein stability and evolution. We show that we can exploit this link to discover protein functions, and we suggest how natural evolution might do the same. 10.1073/pnas.0510098103}, author = {Bloom, Jesse D. and Labthavikul, Sy T. and Otey, Christopher R. and Arnold, Frances H. }, citeulike-article-id = {582306}, doi = {http://dx.doi.org/10.1073/pnas.0510098103}, journal = {PNAS}, keywords = {evolution, protein}, month = {April}, number = {15}, pages = {5869--5874}, posted-at = {2008-01-09 14:21:12}, priority = {3}, title = {Protein stability promotes evolvability}, url = {http://dx.doi.org/10.1073/pnas.0510098103}, volume = {103}, year = {2006} }

RIS record

TY - JOUR ID - citeulike:582306 L3 - citeulike-article-id:582306 N2 - 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 simulations 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 marginally 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 naproxen. Our work establishes a crucial link between protein stability and evolution. We show that we can exploit this link to discover protein functions, and we suggest how natural evolution might do the same. 10.1073/pnas.0510098103 IS - 15 JF - PNAS EP - 5874 TI - Protein stability promotes evolvability VL - 103 SP - 5869 KW - evolution KW - protein AU - Bloom, Jesse AU - Labthavikul, Sy AU - Otey, Christopher AU - Arnold, Frances PY - 2006/04/11/ UR - http://dx.doi.org/10.1073/pnas.0510098103 ER -

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