A Computational Protocol for Regulating Protein Binding Reactions with a Light-Sensitive Protein Dimer

Frank D. Teets, Takashi Watanabe, Klaus M. Hahn, Brian Kuhlman

研究成果: Article査読

5 被引用数 (Scopus)

抄録

Light-sensitive proteins can be used to perturb signaling networks in living cells and animals with high spatiotemporal resolution. We recently engineered a protein heterodimer that dissociates when irradiated with blue light and demonstrated that by fusing each half of the dimer to termini of a protein that it is possible to selectively block binding surfaces on the protein when in the dark. On activation with light, the dimer dissociates and exposes the binding surface, allowing the protein to bind its partner. Critical to the success of this system, called Z-lock, is that the linkers connecting the dimer components to the termini are engineered so that the dimer forms over the appropriate binding surface. Here, we develop and test a protocol in the Rosetta molecular modeling program for designing linkers for Z-lock. We show that the protocol can predict the most effective linker sets for three different light-sensitive switches, including a newly designed switch that binds the Rho-family GTPase Cdc42 on stimulation with blue light. This protocol represents a generalized computational approach to placing a wide variety of proteins under optogenetic control with Z-lock.

本文言語English
ページ(範囲)805-814
ページ数10
ジャーナルJournal of Molecular Biology
432
4
DOI
出版ステータスPublished - 14-02-2020
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 構造生物学
  • 分子生物学

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