Single-particle cryo-EM structural analysis of Q-dependent transcription antitermination
EMSL Project ID
50733
Abstract
The transcription antitermination factor Q, produced by lambdoid bacteriophages, is a textbook example of a regulator of gene expression that functions at the level of transcription termination. Q proteins function by binding to RNA polymerase-DNA-RNA transcription elongation complexes (TECs) and rendering TECs unable to recognize and respond to transcription termination signals.
Q proteins from different lambdoid bacteriophages comprise three different protein families (the Qlambda family, the Q21 family, and the Q82 family), with no detectable sequence similarity to each other and no detectable sequence similarity to other characterized proteins.
Q proteins from different protein families are thought to be analogs (with identical functions but unrelated structures) rather than homologs (with identical functions and related structures).
Q proteins have been the subject of extensive biochemical and genetic analysis spanning five decades. However, an understanding of the structural and mechanistic basis of transcription antitermination by Q proteins has remained elusive in the absence of three-dimensional structural information for Q-dependent antitermination complexes.
We propose to determine high-resolution single-particle-reconstruction cryo-EM structures of Qlambda-, Q21-, and Q82-dependent transcription antitermination complexes.
The availability of three-dimensional structures of Q-dependent transcription antitermination complexes will define the molecular interactions between Q proteins and RNA polymerase and between Q proteins and nucleic acids, and will define the mechanism of Q-dependent transcription antitermination.
The availability of three-dimensional structures of Q-dependent transcription antitermination complexes from all three protein families of lambdoid bacteriophage Q proteins will enable exploration of the remarkable ability of these structurally unrelated protein families to perform analogous biochemical functions.
Programmatic Access is requested (2 years; 9 days on Talos Arctica, preferably starting in the second- or third-quarter of 2019; 31 days on Titan Krios, preferably starting in the third- or fourth-quarter of 2019).
Project Details
Start Date
2019-04-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Wang C., V. Molodtsov, E. Firlar, J.T. Kaelber, G. Blaha, M. Su, and R. Ebright. 2020. "Structural Basis of Transcription-translation Coupling." bioRxiv preprint 369, no. 6509:1359-1365. doi:10.1126/science.abb5317