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

Hanseong Kim, Taisong Zou, Chintan Modi, Katerina Dörner, Timothy J. Grunkemeyer, Liqing Chen, Raimund Fromme, Mikhail V. Matz, Sefika Ozkan, Rebekka Wachter

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)34-43
Number of pages10
JournalStructure
Volume23
Issue number1
DOIs
StatePublished - Jan 6 2015

Fingerprint

Catalytic Domain
Molecular Dynamics Simulation
Articular Range of Motion
Microscopy
Proteins
Phenotype
Light
Mutation
Acids
Enzymes

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 journalArticle

Kim, Hanseong ; Zou, Taisong ; Modi, Chintan ; Dörner, Katerina ; Grunkemeyer, Timothy J. ; Chen, Liqing ; Fromme, Raimund ; Matz, Mikhail V. ; Ozkan, Sefika ; Wachter, Rebekka. / A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins. In: Structure. 2015 ; Vol. 23, No. 1. pp. 34-43.
@article{f8073d85d38f49a387880965f7c22efd,
title = "A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins",
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.",
author = "Hanseong Kim and Taisong Zou and Chintan Modi and Katerina D{\"o}rner and Grunkemeyer, {Timothy J.} and Liqing Chen and Raimund Fromme and Matz, {Mikhail V.} and Sefika Ozkan and Rebekka Wachter",
year = "2015",
month = "1",
day = "6",
doi = "10.1016/j.str.2014.11.011",
language = "English (US)",
volume = "23",
pages = "34--43",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84920973895&partnerID=8YFLogxK

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

VL - 23

SP - 34

EP - 43

JO - Structure with Folding & design

JF - Structure with Folding & design

SN - 0969-2126

IS - 1

ER -