7K1A

TtgR quadruple mutant (C137I I141W M167L F168Y)

Summary for 7K1A

• Entry DOI: 10.2210/pdb7k1a/pdb
• Related: 7K1C 7KD8
• Descriptor: HTH-type transcriptional regulator TtgR, MAGNESIUM ION (3 entities in total)
• Functional Keywords: ttgr, tetr family, epistasis, transcription
• Biological source: Pseudomonas putida
• Total number of polymer chains: 2
• Total formula weight: 48165.63

Authors

Bingman, C.A.,Nishikawa, K.K.,Smith, R.W.,Raman, S. (deposition date: 2020-09-07, release date: 2021-10-06, Last modification date: 2023-10-18)

Primary citation

Nishikawa, K.K.,Hoppe, N.,Smith, R.,Bingman, C.,Raman, S.
Epistasis shapes the fitness landscape of an allosteric specificity switch.
Nat Commun, 12:5562-5562, 2021

PubMed Abstract: Epistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the designed mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. The structure of the designed mutant shows that a striking change in inducer orientation still retains allosteric function. Comparing biophysical and functional properties suggests a nonlinear relationship between inducer binding affinity and allostery. Our results highlight the functional and evolutionary complexity of allosteric proteins.

PubMed: 34548494
DOI: 10.1038/s41467-021-25826-7

Experimental method

X-RAY DIFFRACTION (1.75 Å)