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 journalArticlepeer-review

43 Scopus citations


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
Issue number1
StatePublished - Jan 6 2015

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'A hinge migration mechanism unlocks the evolution of green-to-red photoconversion in GFP-like proteins'. Together they form a unique fingerprint.

Cite this