Structural Basis for the Action of an All-Purpose Transcription Anti-termination Factor.
Mol Cell
; 74(1): 143-157.e5, 2019 04 04.
Article
em En
| MEDLINE
| ID: mdl-30795892
ABSTRACT
Bacteriophage λN protein, a model anti-termination factor, binds nascent RNA and host Nus factors, rendering RNA polymerase resistant to all pause and termination signals. A 3.7-Å-resolution cryo-electron microscopy structure and structure-informed functional analyses reveal a multi-pronged strategy by which the intrinsically unstructured λN directly modifies RNA polymerase interactions with the nucleic acids and subverts essential functions of NusA, NusE, and NusG to reprogram the transcriptional apparatus. λN repositions NusA and remodels the ß subunit flap tip, which likely precludes folding of pause or termination RNA hairpins in the exit tunnel and disrupts termination-supporting interactions of the α subunit C-terminal domains. λN invades and traverses the RNA polymerase hybrid cavity, likely stabilizing the hybrid and impeding pause- or termination-related conformational changes of polymerase. λN also lines upstream DNA, seemingly reinforcing anti-backtracking and anti-swiveling by NusG. Moreover, λN-repositioned NusA and NusE sequester the NusG C-terminal domain, counteracting ρ-dependent termination. Other anti-terminators likely utilize similar mechanisms to enable processive transcription.
Palavras-chave
N proteins of lambdoid phages; Nus factors; RNA polymerase regulation; intrinsic transcription termination; processive transcription anti-termination; single-particle cryo-electron microscopy; structural biology; transcription regulation; transcriptional pausing; ρ-dependent transcription termination
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
RNA Bacteriano
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Bacteriófago lambda
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Escherichia coli
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Proteínas Virais Reguladoras e Acessórias
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Terminação da Transcrição Genética
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article