Helicase Activity Modulation with On-Demand Light-Based Conformational Control

J Am Chem Soc. 2023 Oct 4;145(39):21253-21262. doi: 10.1021/jacs.3c05254. Epub 2023 Sep 22.

Abstract

Engineering a protein variant with a desired role relies on deep knowledge of the relationship between a protein's native structure and function. Using our structural understanding of a regulatory subdomain found in a family of DNA helicases, we engineered novel helicases for which the subdomain orientation is designed to switch between unwinding-inactive and -active conformations upon trans-cis isomerization of an azobenzene-based crosslinker. This on-demand light-based conformational control directly alters helicase activity as demonstrated by both bulk phase experiments and single-molecule optical tweezers analysis of one of the engineered helicases. The "opto-helicase" may be useful in future applications that require spatiotemporal control of DNA hybridization states.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA Helicases* / metabolism
  • DNA, Single-Stranded*
  • Molecular Conformation

Substances

  • DNA Helicases
  • DNA, Single-Stranded