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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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nucleus
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1 term
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Biological process
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regulation of transcription, DNA-dependent
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1 term
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Biochemical function
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transcription factor activity
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2 terms
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Genes Dev
8:2504-2512
(1994)
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PubMed id:
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Crystal structure of a PPR1-DNA complex: DNA recognition by proteins containing a Zn2Cys6 binuclear cluster.
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R.Marmorstein,
S.C.Harrison.
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ABSTRACT
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PPR1 is a yeast transcription factor that contains a six-cysteine, two-zinc (Zn)
domain, homologous to a similar structure in GAL4. Like GAL4, it binds to DNA
sites with conserved CGG triplets symmetrically placed near each end. Whereas
the GAL4 site has 11 intervening base pairs, the PPR1 site has 6. The crystal
structure of a 95-residue fragment of PPR1 in specific complex with DNA shows
that the protein binds to a symmetrical 14-bp recognition site as a
nonsymmetrical homodimer. An amino-terminal Zn domain interacts with a conserved
CGG triplet near each end of the site through major groove contacts, and the
carboxy-terminal residues mediate dimerization through a coiled-coil element and
an extended strand. A linker region, connecting the Zn domain and the
coiled-coil, folds into a beta-hairpin. This hairpin packs differently on the
two subunits and leads to a striking asymmetry, which is largely restricted to
the dimerization and linker regions of the protein. Comparison with the GAL4-DNA
structure shows that their specificities for sites of different length are
determined by the preferred folds of their respective linker segments and by
residues at the amino-terminal ends of their coiled-coils. None of these
residues contact DNA in PPR1, and they contact only the sugar phosphate backbone
in GAL4. We propose that this novel mode of DNA site selection is employed by
other proteins that contain a Zn2Cys6 binuclear cluster.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.R.Stricker,
R.L.Mach,
and
L.H.de Graaff
(2008).
Regulation of transcription of cellulases- and hemicellulases-encoding genes in Aspergillus niger and Hypocrea jecorina (Trichoderma reesei).
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Appl Microbiol Biotechnol, 78,
211-220.
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M.Hong,
M.X.Fitzgerald,
S.Harper,
C.Luo,
D.W.Speicher,
and
R.Marmorstein
(2008).
Structural basis for dimerization in DNA recognition by Gal4.
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Structure, 16,
1019-1026.
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PDB code:
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A.V.Morozov,
and
E.D.Siggia
(2007).
Connecting protein structure with predictions of regulatory sites.
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Proc Natl Acad Sci U S A, 104,
7068-7073.
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E.A.Peroza,
and
E.Freisinger
(2007).
Metal ion binding properties of Triticum [corrected] aestivum Ec-1 metallothionein: evidence supporting two separate metal thiolate clusters.
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J Biol Inorg Chem, 12,
377-391.
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F.Calero-Nieto,
A.Di Pietro,
M.I.Roncero,
and
C.Hera
(2007).
Role of the transcriptional activator xlnR of Fusarium oxysporum in regulation of xylanase genes and virulence.
|
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Mol Plant Microbe Interact, 20,
977-985.
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H.Chen,
M.H.Lee,
M.E.Daub,
and
K.R.Chung
(2007).
Molecular analysis of the cercosporin biosynthetic gene cluster in Cercospora nicotianae.
|
| |
Mol Microbiol, 64,
755-770.
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R.Rauscher,
E.Würleitner,
C.Wacenovsky,
N.Aro,
A.R.Stricker,
S.Zeilinger,
C.P.Kubicek,
M.Penttilä,
and
R.L.Mach
(2006).
Transcriptional regulation of xyn1, encoding xylanase I, in Hypocrea jecorina.
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Eukaryot Cell, 5,
447-456.
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S.MacPherson,
M.Larochelle,
and
B.Turcotte
(2006).
A fungal family of transcriptional regulators: the zinc cluster proteins.
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Microbiol Mol Biol Rev, 70,
583-604.
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S.Maicas,
I.Moreno,
A.Nieto,
M.Gómez,
R.Sentandreu,
and
E.Valentín
(2005).
In Silico Analysis for Transcription Factors With Zn(II)(2)C(6) Binuclear Cluster DNA-Binding Domains in Candida albicans.
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Comp Funct Genomics, 6,
345-356.
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T.Ito,
S.Tani,
T.Itoh,
N.Tsukagoshi,
M.Kato,
and
T.Kobayashi
(2004).
Mode of AmyR binding to the CGGN8AGG sequence in the Aspergillus oryzae taaG2 promoter.
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Biosci Biotechnol Biochem, 68,
1906-1911.
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G.B.Kohlhaw
(2003).
Leucine biosynthesis in fungi: entering metabolism through the back door.
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Microbiol Mol Biol Rev, 67,
1.
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J.H.Kim,
J.Polish,
and
M.Johnston
(2003).
Specificity and regulation of DNA binding by the yeast glucose transporter gene repressor Rgt1.
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Mol Cell Biol, 23,
5208-5216.
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D.Gómez,
B.Cubero,
G.Cecchetto,
and
C.Scazzocchio
(2002).
PrnA, a Zn2Cys6 activator with a unique DNA recognition mode, requires inducer for in vivo binding.
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Mol Microbiol, 44,
585-597.
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J.Avila,
C.González,
N.Brito,
F.Machín,
M.D.Pérez,
and
J.M.Siverio
(2002).
A second Zn(II)(2)Cys(6) transcriptional factor encoded by the YNA2 gene is indispensable for the transcriptional activation of the genes involved in nitrate assimilation in the yeast Hansenula polymorpha.
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Yeast, 19,
537-544.
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M.L.Angus-Hill,
A.Schlichter,
D.Roberts,
H.Erdjument-Bromage,
P.Tempst,
and
B.R.Cairns
(2001).
A Rsc3/Rsc30 zinc cluster dimer reveals novel roles for the chromatin remodeler RSC in gene expression and cell cycle control.
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Mol Cell, 7,
741-751.
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S.Tani,
T.Itoh,
M.Kato,
T.Kobayashi,
and
N.Tsukagoshi
(2001).
In vivo and in vitro analyses of the AmyR binding site of the Aspergillus nidulans agdA promoter; requirement of the CGG direct repeat for induction and high affinity binding of AmyR.
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Biosci Biotechnol Biochem, 65,
1568-1574.
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A.K.Lukens,
D.A.King,
and
R.Marmorstein
(2000).
Structure of HAP1-PC7 bound to DNA: implications for DNA recognition and allosteric effects of DNA-binding on transcriptional activation.
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Nucleic Acids Res, 28,
3853-3863.
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PDB code:
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G.Tsuji,
Y.Kenmochi,
Y.Takano,
J.Sweigard,
L.Farrall,
I.Furusawa,
O.Horino,
and
Y.Kubo
(2000).
Novel fungal transcriptional activators, Cmr1p of Colletotrichum lagenarium and pig1p of Magnaporthe grisea, contain Cys2His2 zinc finger and Zn(II)2Cys6 binuclear cluster DNA-binding motifs and regulate transcription of melanin biosynthesis genes in a developmentally specific manner.
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Mol Microbiol, 38,
940-954.
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A.Kolaczkowska,
and
A.Goffeau
(1999).
Regulation of pleiotropic drug resistance in yeast.
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Drug Resist Updat, 2,
403-414.
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A.Rahner,
M.Hiesinger,
and
H.J.Schüller
(1999).
Deregulation of gluconeogenic structural genes by variants of the transcriptional activator Cat8p of the yeast Saccharomyces cerevisiae.
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Mol Microbiol, 34,
146-156.
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H.Kono,
and
A.Sarai
(1999).
Structure-based prediction of DNA target sites by regulatory proteins.
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Proteins, 35,
114-131.
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I.D.Russell,
A.S.Grancell,
and
P.K.Sorger
(1999).
The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex.
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J Cell Biol, 145,
933-950.
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I.Iraqui,
S.Vissers,
B.André,
and
A.Urrestarazu
(1999).
Transcriptional induction by aromatic amino acids in Saccharomyces cerevisiae.
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Mol Cell Biol, 19,
3360-3371.
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I.Nikolaev,
M.F.Cochet,
F.Lenouvel,
and
B.Felenbok
(1999).
A single amino acid, outside the AlcR zinc binuclear cluster, is involved in DNA binding and in transcriptional regulation of the alc genes in Aspergillus nidulans.
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Mol Microbiol, 31,
1115-1124.
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K.Nadassy,
S.J.Wodak,
and
J.Janin
(1999).
Structural features of protein-nucleic acid recognition sites.
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Biochemistry, 38,
1999-2017.
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P.J.Flynn,
and
R.J.Reece
(1999).
Activation of transcription by metabolic intermediates of the pyrimidine biosynthetic pathway.
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Mol Cell Biol, 19,
882-888.
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S.Kumar,
B.Ma,
C.J.Tsai,
H.Wolfson,
and
R.Nussinov
(1999).
Folding funnels and conformational transitions via hinge-bending motions.
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Cell Biochem Biophys, 31,
141-164.
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B.Cazelle,
A.Pokorska,
E.Hull,
P.M.Green,
G.Stanway,
and
C.Scazzocchio
(1998).
Sequence, exon-intron organization, transcription and mutational analysis of prnA, the gene encoding the transcriptional activator of the prn gene cluster in Aspergillus nidulans.
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Mol Microbiol, 28,
355-370.
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J.Strauss,
M.I.Muro-Pastor,
and
C.Scazzocchio
(1998).
The regulator of nitrate assimilation in ascomycetes is a dimer which binds a nonrepeated, asymmetrical sequence.
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Mol Cell Biol, 18,
1339-1348.
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K.R.Groom,
H.C.Heyman,
M.C.Steffen,
L.Hawkins,
and
N.C.Martin
(1998).
Kluyveromyces lactis SEF1 and its Saccharomyces cerevisiae homologue bypass the unknown essential function, but not the mitochondrial RNase P function, of the S. cerevisiae RPM2 gene.
|
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Yeast, 14,
77-87.
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L.Zhang,
A.Hach,
and
C.Wang
(1998).
Molecular mechanism governing heme signaling in yeast: a higher-order complex mediates heme regulation of the transcriptional activator HAP1.
|
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Mol Cell Biol, 18,
3819-3828.
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N.N.van Peij,
J.Visser,
and
L.H.de Graaff
(1998).
Isolation and analysis of xlnR, encoding a transcriptional activator co-ordinating xylanolytic expression in Aspergillus niger.
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Mol Microbiol, 27,
131-142.
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R.B.Todd,
A.Andrianopoulos,
M.A.Davis,
and
M.J.Hynes
(1998).
FacB, the Aspergillus nidulans activator of acetate utilization genes, binds dissimilar DNA sequences.
|
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EMBO J, 17,
2042-2054.
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T.S.Heuer,
and
P.O.Brown
(1998).
Photo-cross-linking studies suggest a model for the architecture of an active human immunodeficiency virus type 1 integrase-DNA complex.
|
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Biochemistry, 37,
6667-6678.
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A.L.Vuidepot,
F.Bontems,
M.Gervais,
B.Guiard,
E.Shechter,
and
J.Y.Lallemand
(1997).
NMR analysis of CYP1(HAP1) DNA binding domain-CYC1 upstream activation sequence interactions: recognition of a CGG trinucleotide and of an additional thymine 5 bp downstream by the zinc cluster and the N-terminal extremity of the protein.
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Nucleic Acids Res, 25,
3042-3050.
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D.H.Sweet,
Y.K.Jang,
and
G.B.Sancar
(1997).
Role of UME6 in transcriptional regulation of a DNA repair gene in Saccharomyces cerevisiae.
|
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Mol Cell Biol, 17,
6223-6235.
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G.Patikoglou,
and
S.K.Burley
(1997).
Eukaryotic transcription factor-DNA complexes.
|
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Annu Rev Biophys Biomol Struct, 26,
289-325.
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H.Rottensteiner,
A.J.Kal,
B.Hamilton,
H.Ruis,
and
H.F.Tabak
(1997).
A heterodimer of the Zn2Cys6 transcription factors Pip2p and Oaf1p controls induction of genes encoding peroxisomal proteins in Saccharomyces cerevisiae.
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Eur J Biochem, 247,
776-783.
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J.A.Graden,
and
D.R.Winge
(1997).
Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor.
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Proc Natl Acad Sci U S A, 94,
5550-5555.
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J.W.Schwabe,
and
D.Rhodes
(1997).
Linkers made to measure.
|
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Nat Struct Biol, 4,
680-683.
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K.J.Walters,
K.T.Dayie,
R.J.Reece,
M.Ptashne,
and
G.Wagner
(1997).
Structure and mobility of the PUT3 dimer.
|
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Nat Struct Biol, 4,
744-750.
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PDB code:
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K.Swaminathan,
P.Flynn,
R.J.Reece,
and
R.Marmorstein
(1997).
Crystal structure of a PUT3-DNA complex reveals a novel mechanism for DNA recognition by a protein containing a Zn2Cys6 binuclear cluster.
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Nat Struct Biol, 4,
751-759.
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PDB code:
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R.Näit-Kaoudjt,
R.Williams,
B.Guiard,
and
M.Gervais
(1997).
Some DNA targets of the yeast CYP1 transcriptional activator are functionally asymmetric--evidence of two half-sites with different affinities.
|
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Eur J Biochem, 244,
301-309.
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S.F.Bellon,
K.K.Rodgers,
D.G.Schatz,
J.E.Coleman,
and
T.A.Steitz
(1997).
Crystal structure of the RAG1 dimerization domain reveals multiple zinc-binding motifs including a novel zinc binuclear cluster.
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Nat Struct Biol, 4,
586-591.
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PDB code:
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H.Rottensteiner,
A.J.Kal,
M.Filipits,
M.Binder,
B.Hamilton,
H.F.Tabak,
and
H.Ruis
(1996).
Pip2p: a transcriptional regulator of peroxisome proliferation in the yeast Saccharomyces cerevisiae.
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EMBO J, 15,
2924-2934.
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K.Hellauer,
M.H.Rochon,
and
B.Turcotte
(1996).
A novel DNA binding motif for yeast zinc cluster proteins: the Leu3p and Pdr3p transcriptional activators recognize everted repeats.
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Mol Cell Biol, 16,
6096-6102.
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L.Zhang,
and
L.Guarente
(1996).
The C6 zinc cluster dictates asymmetric binding by HAP1.
|
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EMBO J, 15,
4676-4681.
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P.Schjerling,
and
S.Holmberg
(1996).
Comparative amino acid sequence analysis of the C6 zinc cluster family of transcriptional regulators.
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Nucleic Acids Res, 24,
4599-4607.
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S.D.Liang,
R.Marmorstein,
S.C.Harrison,
and
M.Ptashne
(1996).
DNA sequence preferences of GAL4 and PPR1: how a subset of Zn2 Cys6 binuclear cluster proteins recognizes DNA.
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Mol Cell Biol, 16,
3773-3780.
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W.M.Gray,
and
J.S.Fassler
(1996).
Isolation and analysis of the yeast TEA1 gene, which encodes a zinc cluster Ty enhancer-binding protein.
|
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Mol Cell Biol, 16,
347-358.
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A.Barberis,
J.Pearlberg,
N.Simkovich,
S.Farrell,
P.Reinagel,
C.Bamdad,
G.Sigal,
and
M.Ptashne
(1995).
Contact with a component of the polymerase II holoenzyme suffices for gene activation.
|
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Cell, 81,
359-368.
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K.H.Gardner,
S.F.Anderson,
and
J.E.Coleman
(1995).
Solution structure of the Kluyveromyces lactis LAC9 Cd2 Cys6 DNA-binding domain.
|
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Nat Struct Biol, 2,
898-905.
|
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PDB code:
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S.F.Anderson,
C.M.Steber,
R.E.Esposito,
and
J.E.Coleman
(1995).
UME6, a negative regulator of meiosis in Saccharomyces cerevisiae, contains a C-terminal Zn2Cys6 binuclear cluster that binds the URS1 DNA sequence in a zinc-dependent manner.
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Protein Sci, 4,
1832-1843.
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S.Yanagisawa
(1995).
A novel DNA-binding domain that may form a single zinc finger motif.
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Nucleic Acids Res, 23,
3403-3410.
|
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T.Suárez,
M.V.de Queiroz,
N.Oestreicher,
and
C.Scazzocchio
(1995).
The sequence and binding specificity of UaY, the specific regulator of the purine utilization pathway in Aspergillus nidulans, suggest an evolutionary relationship with the PPR1 protein of Saccharomyces cerevisiae.
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| |
EMBO J, 14,
1453-1467.
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V.V.Svetlov,
and
T.G.Cooper
(1995).
Review: compilation and characteristics of dedicated transcription factors in Saccharomyces cerevisiae.
|
| |
Yeast, 11,
1439-1484.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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