A Full-Length Group 1 Bacterial Sigma Factor Adopts a Compact Structure Incompatible with DNA Binding

Edmund C. Schwartz; Alexander Shekhtman; Kaushik Dutta; Matthew R. Pratt; David Cowburn; Seth Darst; Tom W. Muir

doi:10.1016/j.chembiol.2008.09.008

A Full-Length Group 1 Bacterial Sigma Factor Adopts a Compact Structure Incompatible with DNA Binding

Edmund C. Schwartz, Alexander Shekhtman, Kaushik Dutta, Matthew R. Pratt, David Cowburn, Seth Darst, Tom W. Muir

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

The σ factors are the key regulators of bacterial transcription initiation. Through direct read-out of promoter DNA sequence, they recruit the core RNA polymerase to sites of initiation, thereby dictating the RNA polymerase promoter-specificity. The group 1 σ factors, which direct the vast majority of transcription initiation during log phase growth and are essential for viability, are autoregulated by an N-terminal sequence known as σ_1.1. We report the solution structure of Thermotoga maritima σ^A σ_1.1. We additionally demonstrate by using chemical crosslinking strategies that σ_1.1 is in close proximity to the promoter recognition domains of σ^A. We therefore propose that σ_1.1 autoinhibits promoter DNA binding of free σ^A by stabilizing a compact organization of the σ factor domains that is unable to bind DNA.

Original language	English (US)
Pages (from-to)	1091-1103
Number of pages	13
Journal	Chemistry and Biology
Volume	15
Issue number	10
DOIs	https://doi.org/10.1016/j.chembiol.2008.09.008
State	Published - Oct 20 2008
Externally published	Yes

All Science Journal Classification (ASJC) codes

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmacology

Keywords

CHEMBIO
DNA

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10.1016/j.chembiol.2008.09.008

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title = "A Full-Length Group 1 Bacterial Sigma Factor Adopts a Compact Structure Incompatible with DNA Binding",

abstract = "The σ factors are the key regulators of bacterial transcription initiation. Through direct read-out of promoter DNA sequence, they recruit the core RNA polymerase to sites of initiation, thereby dictating the RNA polymerase promoter-specificity. The group 1 σ factors, which direct the vast majority of transcription initiation during log phase growth and are essential for viability, are autoregulated by an N-terminal sequence known as σ1.1. We report the solution structure of Thermotoga maritima σA σ1.1. We additionally demonstrate by using chemical crosslinking strategies that σ1.1 is in close proximity to the promoter recognition domains of σA. We therefore propose that σ1.1 autoinhibits promoter DNA binding of free σA by stabilizing a compact organization of the σ factor domains that is unable to bind DNA.",

keywords = "CHEMBIO, DNA",

author = "Schwartz, {Edmund C.} and Alexander Shekhtman and Kaushik Dutta and Pratt, {Matthew R.} and David Cowburn and Seth Darst and Muir, {Tom W.}",

note = "Funding Information: This work was supported by National Institutes of Health Grants GM 053759-10 (T.W.M., S.A.D.), GM55843-11 (T.W.M.) and EB-001991 (T.W.M.) and by a Howard Hughes Medical Institute fellowship (E.C.S.). NMR resources at NYSBC are supported by P41 GM66354. We thank Lars Westblade and Andrey Feklistov for technical assistance. ",

year = "2008",

month = oct,

day = "20",

doi = "10.1016/j.chembiol.2008.09.008",

language = "English (US)",

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pages = "1091--1103",

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T1 - A Full-Length Group 1 Bacterial Sigma Factor Adopts a Compact Structure Incompatible with DNA Binding

AU - Schwartz, Edmund C.

AU - Shekhtman, Alexander

AU - Dutta, Kaushik

AU - Pratt, Matthew R.

AU - Cowburn, David

AU - Darst, Seth

AU - Muir, Tom W.

N1 - Funding Information: This work was supported by National Institutes of Health Grants GM 053759-10 (T.W.M., S.A.D.), GM55843-11 (T.W.M.) and EB-001991 (T.W.M.) and by a Howard Hughes Medical Institute fellowship (E.C.S.). NMR resources at NYSBC are supported by P41 GM66354. We thank Lars Westblade and Andrey Feklistov for technical assistance.

PY - 2008/10/20

Y1 - 2008/10/20

N2 - The σ factors are the key regulators of bacterial transcription initiation. Through direct read-out of promoter DNA sequence, they recruit the core RNA polymerase to sites of initiation, thereby dictating the RNA polymerase promoter-specificity. The group 1 σ factors, which direct the vast majority of transcription initiation during log phase growth and are essential for viability, are autoregulated by an N-terminal sequence known as σ1.1. We report the solution structure of Thermotoga maritima σA σ1.1. We additionally demonstrate by using chemical crosslinking strategies that σ1.1 is in close proximity to the promoter recognition domains of σA. We therefore propose that σ1.1 autoinhibits promoter DNA binding of free σA by stabilizing a compact organization of the σ factor domains that is unable to bind DNA.

AB - The σ factors are the key regulators of bacterial transcription initiation. Through direct read-out of promoter DNA sequence, they recruit the core RNA polymerase to sites of initiation, thereby dictating the RNA polymerase promoter-specificity. The group 1 σ factors, which direct the vast majority of transcription initiation during log phase growth and are essential for viability, are autoregulated by an N-terminal sequence known as σ1.1. We report the solution structure of Thermotoga maritima σA σ1.1. We additionally demonstrate by using chemical crosslinking strategies that σ1.1 is in close proximity to the promoter recognition domains of σA. We therefore propose that σ1.1 autoinhibits promoter DNA binding of free σA by stabilizing a compact organization of the σ factor domains that is unable to bind DNA.

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KW - DNA

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A Full-Length Group 1 Bacterial Sigma Factor Adopts a Compact Structure Incompatible with DNA Binding

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