Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx

Wael Awad, Yusra Al-Eryani, Simon Ekström, Derek T. Logan, Claes von Wachenfeldt

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

YjbH is a bacterial adaptor protein required for efficient proteolysis of the RNA polymerase-binding transcription factor Spx by the ClpXP protease. We report the structure of YjbH in complex with Spx. YjbH comprises a DsbA-like thioredoxin domain connected via a linker to a C-terminal domain reminiscent of the winged helix-turn-helix fold. The interaction between YjbH and Spx involves a large surface area. Binding to YjbH stabilizes the C-terminal ClpX recognition region of Spx. We show that mutation of critical YjbH contact residues abrogates Spx recognition. Small-angle X-ray scattering and hydrogen-deuterium exchange mass spectrometry analyses determined the existence of a stable heterodimeric complex in solution and provide evidence that binding of Spx to YjbH reduces the overall conformational flexibility of Spx. Our findings provide insights into the molecular basis for Spx recognition and suggest a model for how YjbH stabilizes Spx and displays the C terminus of Spx for engagement by ClpXP. Awad et al. determined the crystal structure of the ClpXP adaptor protein YjbH in complex with the transcription factor Spx. Structural dynamics of the complex were investigated by hydrogen-deuterium exchange mass spectrometry. The insights provided in this work add molecular details to the recognition of Spx by YjbH.

Original languageEnglish
Pages (from-to)923-936
Number of pages14
JournalStructure
Volume27
Issue number6
DOIs
Publication statusPublished - 4 Jun 2019
Externally publishedYes

Keywords

  • adaptor protein
  • ClpXP
  • proteolysis
  • Spx
  • stress response
  • YjbH

Cite this

Awad, W., Al-Eryani, Y., Ekström, S., Logan, D. T., & von Wachenfeldt, C. (2019). Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx. Structure, 27(6), 923-936. https://doi.org/10.1016/j.str.2019.03.009