In proteins, functional divergence involves mutations that modify structure and dynamics. Here we provide experimental evidence for an evolutionary mechanism driven solely by long-range dynamic motions without significant backbone adjustments, catalytic group rearrangements, or changes in subunit assembly. Crystallographic structures were determined for several reconstructed ancestral proteins belonging to a GFP class frequently employed in superresolution microscopy. Their chain flexibility was analyzed using molecular dynamics and perturbation response scanning. The green-to-red photoconvertible phenotype appears to have arisen from a common green ancestor by migration of a knob-like anchoring region away from the active site diagonally across the β barrel fold. The allosterically coupled mutational sites provide active site conformational mobility via epistasis. We propose that light-induced chromophore twisting is enhanced in a reverse-protonated subpopulation, activating internal acid-base chemistry and backbone cleavage to enlarge the chromophore. Dynamics-driven hinge migration may represent a more general platform for the evolution of novel enzyme activities.
Details
- A Hinge Migration Mechanism Unlocks the Evolution of Green-to-Red Photoconversion in GFP-Like Proteins
- Kim, Hanseong (Author)
- Zou, Taisong (Author)
- Modi, Chintan (Author)
- Dorner, Katerina (Author)
- Grunkemeyer, Timothy (Author)
- Chen, Liqing (Author)
- Fromme, Raimund (Author)
- Matz, Mikhail V. (Author)
- Ozkan, Sefika (Author)
- Wachter, Rebekka (Author)
- Department of Chemistry and Biochemistry (Contributor)
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Digital object identifier: 10.1016/j.str.2014.11.011
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Identifier TypeInternational standard serial numberIdentifier Value0969-2126
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This is the authors' final, accepted manuscript. The final version as published is available at http://dx.doi.org/10.1016/j.str.2014.11.011
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Kim, Hanseong, Zou, Taisong, Modi, Chintan, Doerner, Katerina, Grunkemeyer, Timothy J., Chen, Liqing, Fromme, Raimund, Matz, Mikhail V., Ozkan, S. Banu, & Wachter, Rebekka M. (2015). A Hinge Migration Mechanism Unlocks the Evolution of Green-to-Red Photoconversion in GFP-like Proteins. STRUCTURE, 23(1), 34-43. http://dx.doi.org/10.1016/j.str.2014.11.011