The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR

Daan M.F. Van Aalten, Concetta C DiRusso, Jens Knudsen

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA. The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule >30 Å away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 Å. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Å in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.

Original languageEnglish (US)
Pages (from-to)2041-2050
Number of pages10
JournalEMBO Journal
Volume20
Issue number8
DOIs
StatePublished - Apr 17 2001

Fingerprint

Acyl Coenzyme A
Transcription Factors
DNA
Proteins
Gene Rearrangement
Dimers
Escherichia coli
Fatty Acids
Binding Sites
Genes
Degradation
Molecules

Keywords

  • Acyl-CoA
  • Fatty acid
  • Protein structure
  • Regulation
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR. / Van Aalten, Daan M.F.; DiRusso, Concetta C; Knudsen, Jens.

In: EMBO Journal, Vol. 20, No. 8, 17.04.2001, p. 2041-2050.

Research output: Contribution to journalArticle

Van Aalten, Daan M.F. ; DiRusso, Concetta C ; Knudsen, Jens. / The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR. In: EMBO Journal. 2001 ; Vol. 20, No. 8. pp. 2041-2050.
@article{be00434721d64b9a833b299e18f5f9f0,
title = "The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR",
abstract = "FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA. The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule >30 {\AA} away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 {\AA}. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 {\AA} in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.",
keywords = "Acyl-CoA, Fatty acid, Protein structure, Regulation, Transcription",
author = "{Van Aalten}, {Daan M.F.} and DiRusso, {Concetta C} and Jens Knudsen",
year = "2001",
month = "4",
day = "17",
doi = "10.1093/emboj/20.8.2041",
language = "English (US)",
volume = "20",
pages = "2041--2050",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - The structural basis of acyl coenzyme A-dependent regulation of the transcription factor FadR

AU - Van Aalten, Daan M.F.

AU - DiRusso, Concetta C

AU - Knudsen, Jens

PY - 2001/4/17

Y1 - 2001/4/17

N2 - FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA. The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule >30 Å away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 Å. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Å in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.

AB - FadR is an acyl-CoA-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli. The apo-protein binds DNA as a homodimer, an interaction that is disrupted by binding of acyl-CoA. The recently described structure of apo-FadR shows a DNA binding domain coupled to an acyl-CoA binding domain with a novel fold, but does not explain how binding of the acyl-CoA effector molecule >30 Å away from the DNA binding site affects transcriptional regulation. Here, we describe the structures of the FadR-operator and FadR-myristoyl-CoA binary complexes. The FadR-DNA complex reveals a novel winged helix-turn-helix protein-DNA interaction, involving sequence-specific contacts from the wing to the minor groove. Binding of acyl-CoA results in dramatic conformational changes throughout the protein, with backbone shifts up to 4.5 Å. The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Å in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.

KW - Acyl-CoA

KW - Fatty acid

KW - Protein structure

KW - Regulation

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=0035901537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035901537&partnerID=8YFLogxK

U2 - 10.1093/emboj/20.8.2041

DO - 10.1093/emboj/20.8.2041

M3 - Article

VL - 20

SP - 2041

EP - 2050

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 8

ER -