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) |
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Pages (from-to) | 34-43 |
Number of pages | 10 |
Journal | Structure |
Volume | 23 |
Issue number | 1 |
DOIs | |
State | Published - Jan 6 2015 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
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Crystal Structure of an Ancestor of All Faviina Proteins
Kim, H. (Contributor), Zou, T. (Contributor), Modi, C. (Contributor), Dörner, K. (Contributor), Grunkemeyer, T. J. (Contributor), Chen, L. (Contributor), Fromme, R. (Contributor), Matz, M. V. (Contributor), Ozkan, B. (Contributor) & Wachter, R. M. (Contributor), Protein Data Bank (PDB), Feb 27 2013
DOI: 10.2210/pdb4DXI, https://www.wwpdb.org/pdb?id=pdb_00004dxi
Dataset
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Crystal Structure of a reconstructed Kaede-type Red Fluorescent Protein, LEA X121
Kim, H. (Contributor), Zou, T. (Contributor), Modi, C. (Contributor), Dörner, K. (Contributor), Grunkemeyer, T. J. (Contributor), Chen, L. (Contributor), Fromme, R. (Contributor), Matz, M. V. (Contributor), Ozkan, B. (Contributor) & Wachter, R. M. (Contributor), Protein Data Bank (PDB), Feb 27 2013
DOI: 10.2210/pdb4DXP, https://www.wwpdb.org/pdb?id=pdb_00004dxp
Dataset
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Crystal Structure of an ancestral GFP-like protein
Kim, H. (Contributor), Zou, T. (Contributor), Modi, C. (Contributor), Dörner, K. (Contributor), Grunkemeyer, T. J. (Contributor), Chen, L. (Contributor), Fromme, R. (Contributor), Matz, M. V. (Contributor), Ozkan, B. (Contributor) & Wachter, R. M. (Contributor), Protein Data Bank (PDB), Feb 27 2013
DOI: 10.2210/pdb4DXM, https://www.wwpdb.org/pdb?id=pdb_00004dxm
Dataset