Balancing between affinity and speed in target DNA search by zinc-finger proteins via modulation of dynamic conformational ensemble

• DOI: 10.1073/pnas.1507726112
• Publication Date: 2015-09-01T02:19:53Z
• Authors: Levani Zandarashvili; Alexandre Esadze; Dana Vuzman; Catherine A. Kemme; Yaakov Levy; Junji Iwahara
• Keywords: Nuclease; Zinc finger nuclease; Protein–DNA interaction

Significance Many transcription factors and DNA repair/modifying enzymes must first locate the target sites through stochastic scanning of in vast presence nonspecific sites. In this work, we demonstrate that search by these proteins can be accelerated via engineering based on structural dynamic knowledge DNA-scanning process. Our biophysical data for Egr-1 zinc-finger protein its nuclease derivatives reveal kinetic thermodynamic roles conformational equilibrium between two modes process: one suitable other recognition. We found optimizing balance recognition improves efficiency proteins’ search. This finding help advance technology artificial gene regulation genome editing.