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

被引:130
作者
van Aalten, DMF
Dirusso, CC
Knudsen, J
机构
[1] Univ Dundee, Sch Life Sci, Div Biol Chem & Mol Microbiol, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland
[2] Albany Med Coll, Ctr Cardiovac Sci, Albany, NY 12208 USA
[3] Odense Univ, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark
基金
英国惠康基金;
关键词
acyl-CoA; fatty acid; protein structure; regulation; transcription;
D O I
10.1093/emboj/20.8.2041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
FadR is an acyl-Coh-responsive transcription factor, regulating fatty acid biosynthetic and degradation genes in Escherichia coli, The ape-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 Angstrom 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 Angstrom, The net effect is a rearrangement of the DNA binding domains in the dimer, resulting in a change of 7.2 Angstrom in separation of the DNA recognition helices and the loss of DNA binding, revealing the molecular basis of acyl-CoA-responsive regulation.
引用
收藏
页码:2041 / 2050
页数:10
相关论文
共 37 条
[1]  
Bell CE, 2000, NAT STRUCT BIOL, V7, P209
[2]   Crystallography & NMR system:: A new software suite for macromolecular structure determination [J].
Brunger, AT ;
Adams, PD ;
Clore, GM ;
DeLano, WL ;
Gros, P ;
Grosse-Kunstleve, RW ;
Jiang, JS ;
Kuszewski, J ;
Nilges, M ;
Pannu, NS ;
Read, RJ ;
Rice, LM ;
Simonson, T ;
Warren, GL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 :905-921
[3]   CooA, CAP and allostery [J].
Chan, MK .
NATURE STRUCTURAL BIOLOGY, 2000, 7 (10) :822-824
[4]   Molecular inroads into the regulation and metabolism of fatty acids, lessons from bacteria [J].
DiRusso, CC ;
Black, PN ;
Weimar, JD .
PROGRESS IN LIPID RESEARCH, 1999, 38 (02) :129-197
[5]   Fatty Acyl-CoA binding domain of the transcription factor FadR - Characterization by deletion, affinity labeling, and isothermal titration calorimetry [J].
DiRusso, CC ;
Tsvetnitsky, V ;
Hojrup, P ;
Knudsen, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (50) :33652-33659
[6]   REGULATION OF TRANSCRIPTION OF GENES REQUIRED FOR FATTY-ACID TRANSPORT AND UNSATURATED FATTY-ACID BIOSYNTHESIS IN ESCHERICHIA-COLI BY FADR [J].
DIRUSSO, CC ;
METZGER, AK ;
HEIMERT, TL .
MOLECULAR MICROBIOLOGY, 1993, 7 (02) :311-322
[7]  
DIRUSSO CC, 1992, J BIOL CHEM, V267, P8685
[8]   Crystal structure of the human RXRα ligand-binding domain bound to its natural ligand:: 9-cis retinoic acid [J].
Egea, PF ;
Mitschler, A ;
Rochel, N ;
Ruff, M ;
Chambon, P ;
Moras, D .
EMBO JOURNAL, 2000, 19 (11) :2592-2601
[9]   The diverse world of coenzyme A binding proteins [J].
Engel, C ;
Wierenga, R .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1996, 6 (06) :790-797
[10]   CRYSTAL-STRUCTURE OF LAC REPRESSOR CORE TETRAMER AND ITS IMPLICATIONS FOR DNA LOOPING [J].
FRIEDMAN, AM ;
FISCHMANN, TO ;
STEITZ, TA .
SCIENCE, 1995, 268 (5218) :1721-1727