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PDBsum entry 3bts
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protein ligands Protein-protein interface(s) links
Transcription PDB id
3bts

 

 

 

 

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Contents
Protein chains
384 a.a. *
Ligands
MET-PHE-ASN-THR-
THR-THR-MET-ASP-
ASP
THR-THR-MET-ASP-
ASP
NAD ×2
Waters ×127
* Residue conservation analysis
PDB id:
3bts
Name: Transcription
Title: Crystal structure of a ternary complex of the transcriptional repressor gal80p (gal80s0 [g301r]) and the acidic activation domain of gal4p (aa 854-874) from saccharomyces cerevisiae with NAD
Structure: Galactose/lactose metabolism regulatory protein gal80. Chain: a, b. Engineered: yes. Mutation: yes. Regulatory protein gal4. Chain: e, f. Fragment: s. Cerevisiae gal4p peptide. Unp residues 854-874. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: gal80. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: s.Cerevisiae gal4(854-874) was made synthetically
Resolution:
2.70Å     R-factor:   0.175     R-free:   0.232
Authors: P.R.Kumar,L.Joshua-Tor
Key ref:
P.R.Kumar et al. (2008). NADP regulates the yeast GAL induction system. Science, 319, 1090-1092. PubMed id: 18292341 DOI: 10.1126/science.1151903
Date:
30-Dec-07     Release date:   04-Mar-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04387  (GAL80_YEAST) -  Galactose/lactose metabolism regulatory protein GAL80 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		435 a.a.
384 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1126/science.1151903 Science 319:1090-1092 (2008)
PubMed id: 18292341  
 
 
NADP regulates the yeast GAL induction system.
P.R.Kumar, Y.Yu, R.Sternglanz, S.A.Johnston, L.Joshua-Tor.
 
  ABSTRACT  
 
Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UAS(GAL)); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial induction event.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. (A) Two views of the ScGal80p^S0-ScGal4AD-NAD dimer. The bottom view is rotated 90° around the horizontal axis compared to the top view. ScGal80p is depicted as gray ribbons, and the Gal4p-AD peptide and the NAD are shown in stick form (Gal4p-AD peptide: purple; NAD atoms: yellow, carbon; red, oxygen; blue, nitrogen; and green, phosphorus). Disordered regions are shown as a dashed coil. The β-sheet regions of the C-terminal domains form an extensive dimeric interface. (B) NAD binding. Hydrogen-bonding interactions involving the NAD dinucleotide are shown as dashed lines with the corresponding distances indicated (Å). The side chain of W31 stacks on the NAD nicotinamide ring. Atoms are color-coded as in (A) with Gal80p carbons in gray, NAD carbons in yellow, and the Gal4p-AD peptide carbons in purple (7). 		Figure 3.
Fig. 3. Alterations in the NADP binding site changes the rate of induction in vivo. GAL1 mRNA expression as a function of time after galactose induction. Data are shown for wild-type Gal80p and for Gal80p point mutants. All data were normalized to RNA levels measured for a control gene, PMA1. A gal80 mutant has a high expression level even when uninduced—as high as that seen for wild-type Gal80p when fully induced. The dimer mutant, N230R, also shows expression in the uninduced state (SOM text).
 
  The above figures are reprinted from an Open Access publication published by the AAAs: Science (2008, 319, 1090-1092) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20513431 K.J.McLaughlin, C.M.Strain-Damerell, K.Xie, D.Brekasis, A.S.Soares, M.S.Paget, and C.L.Kielkopf (2010).
Structural basis for NADH/NAD+ redox sensing by a Rex family repressor.
  Mol Cell, 38, 563-575.
PDB codes: 3ikt 3ikv 3il2
20124348 M.L.Ginger, G.I.McFadden, and P.A.Michels (2010).
Rewiring and regulation of cross-compartmentalized metabolism in protists.
  Philos Trans R Soc Lond B Biol Sci, 365, 831-845.  
21115813 R.A.Wilson, R.P.Gibson, C.F.Quispe, J.A.Littlechild, and N.J.Talbot (2010).
An NADPH-dependent genetic switch regulates plant infection by the rice blast fungus.
  Proc Natl Acad Sci U S A, 107, 21902-21907.  
20506376 X.Zhao, S.L.Hume, C.Johnson, P.Thompson, J.Huang, J.Gray, H.K.Lamb, and A.R.Hawkins (2010).
The transcription repressor NmrA is subject to proteolysis by three Aspergillus nidulans proteases.
  Protein Sci, 19, 1405-1419.  
20979343 Y.Li, G.Chen, and W.Liu (2010).
Multiple metabolic signals influence GAL gene activation by modulating the interaction of Gal80p with the transcriptional activator Gal4p.
  Mol Microbiol, 78, 414-428.  
19894711 B.A.Williams, C.W.Diehnelt, P.Belcher, M.Greving, N.W.Woodbury, S.A.Johnston, and J.C.Chaput (2009).
Creating protein affinity reagents by combining peptide ligands on synthetic DNA scaffolds.
  J Am Chem Soc, 131, 17233-17241.  
18772282 E.Nevoigt (2008).
Progress in metabolic engineering of Saccharomyces cerevisiae.
  Microbiol Mol Biol Rev, 72, 379-412.  
18701455 J.B.Thoden, L.A.Ryan, R.J.Reece, and H.M.Holden (2008).
The interaction between an acidic transcriptional activator and its inhibitor. The molecular basis of Gal4p recognition by Gal80p.
  J Biol Chem, 283, 30266-30272.
PDB code: 3e1k
19061643 J.Houseley, L.Rubbi, M.Grunstein, D.Tollervey, and M.Vogelauer (2008).
A ncRNA modulates histone modification and mRNA induction in the yeast GAL gene cluster.
  Mol Cell, 32, 685-695.  
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 codes are shown on the right.

 

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