TY - JOUR
T1 - A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins
AU - Kim, Hanseong
AU - Zou, Taisong
AU - Modi, Chintan
AU - Dörner, Katerina
AU - Grunkemeyer, Timothy J.
AU - Chen, Liqing
AU - Fromme, Raimund
AU - Matz, Mikhail V.
AU - Ozkan, Sefika
AU - Wachter, Rebekka
PY - 2015/1/6
Y1 - 2015/1/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2014.11.011
DO - 10.1016/j.str.2014.11.011
M3 - Article
C2 - 25565105
AN - SCOPUS:84920973895
VL - 23
SP - 34
EP - 43
JO - Structure with Folding & design
JF - Structure with Folding & design
SN - 0969-2126
IS - 1
ER -