Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 34-43 |
| Number of pages | 10 |
| Journal | Structure |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 6 2015 |
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ASJC Scopus subject areas
- Molecular Biology
- Structural Biology
Cite this
A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins. / Kim, Hanseong; Zou, Taisong; Modi, Chintan; Dörner, Katerina; Grunkemeyer, Timothy J.; Chen, Liqing; Fromme, Raimund; Matz, Mikhail V.; Ozkan, Sefika; Wachter, Rebekka.
In: Structure, Vol. 23, No. 1, 06.01.2015, p. 34-43.Research output: Contribution to journal › Article
}
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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UR - http://www.scopus.com/inward/citedby.url?scp=84920973895&partnerID=8YFLogxK
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 -