A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins.

A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins.
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DOI:
10.1016/j.str.2014.11.011
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发表时间:
2015-01-06
期刊:
影响因子:
5.7
通讯作者:
Wachter, Rebekka M.
Wachter, Rebekka M.
中科院分区:
生物学2区
文献类型:
--
作者:
Kim, Hanseong;Zou, Taisong;Modi, Chintan;Doerner, Katerina;Grunkemeyer, Timothy J.;Chen, Liqing;Fromme, Raimund;Matz, Mikhail V.;Ozkan, S. Banu;Wachter, Rebekka M.

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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-tored 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 beta-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.
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