S. A. Darst

Early intermediates in bacterial RNA polymerase promoter melting visualized by time-resolved cryo-electron microscopy

This study uses time-resolved cryo-EM to visualize early intermediates in bacterial RNA polymerase promoter melting, revealing key steps in the formation of the transcription-competent open complex.

Molecular switching of a DNA-sliding clamp to a repressor mediates long-range gene silencing

The paper shows that KorB, a DNA-sliding clamp, switches to a repressor role with KorA to mediate long-range gene silencing on plasmid RK2.

Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain

This study determines cryo-EM structures of SARS-CoV-2 NiRAN domain catalytic intermediates, revealing structural mechanisms for NMPylation and deRNAylation/capping, and explaining substrate preference for capping.

Discovery, Characterization, and Bioactivity of the Achromonodins: Lasso Peptides Encoded by Achromobacter

The paper discovers and characterizes two lasso peptides from Achromobacter species, showing one inhibits RNA polymerase and has antimicrobial activity against Achromobacter pulmonis.

An ensemble of interconverting conformations of the elemental paused transcription complex creates regulatory options

This study defines an interconverting ensemble of ePEC states using cryo-EM and biochemical analysis, showing that ePECs occupy pre- or half-translocated states without always swiveling.

Structural basis for substrate selection by the SARS-CoV-2 replicase

This study uses cryo-EM to reveal how the SARS-CoV-2 RTC discriminates between natural NTPs and the antiviral remdesivir triphosphate, providing insights for antiviral design.

Ensemble cryo-electron microscopy reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex

This study uses cryo-EM and simulations to identify four conformational states of the nsp13 helicase in the SARS-CoV-2 RTC, revealing an allosteric mechanism for switching between RNA synthesis and backtracking.

Structural origins of Escherichia coli RNA polymerase open promoter complex stability

This study determines the structural basis of RNA polymerase open complex stability in E. coli by analyzing three promoters with different lifetimes using cryo-EM.

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex

This paper shows that SARS-CoV-2 RdRp undergoes backtracking, which may aid proofreading and antiviral resistance.

Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex

The paper presents cryo-EM structures of the SARS-CoV-2 holo-RdRp complex with nsp13 helicase, revealing interactions and a new therapeutic target.

Structural basis for transcription complex disruption by the Mfd translocase

The paper uses cryo-EM to visualize Mfd interacting with stalled RNA polymerase complexes, revealing its mechanism for initiating transcription-coupled repair.

E. coli TraR allosterically regulates transcription initiation by altering RNA polymerase conformation and dynamics

This study shows TraR regulates transcription by altering RNAP conformation and dynamics, affecting promoter DNA interactions and transcription outcomes.

Structural basis for transcription activation by Crl through tethering of σS and RNA polymerase

The paper determines the cryo-EM structure of Crl-σS-RNAP complex and shows Crl stabilizes σS-RNAP by tethering σS to RNAP βCT.

Fidaxomicin jams M. tuberculosis RNA polymerase motions needed for initiation via RbpA contacts

This study determines the structure of M. tuberculosis RNA polymerase with fidaxomicin, revealing how it inhibits transcription by blocking essential motions.