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PDBsum entry 2f9g

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protein ligands metals links
Transferase PDB id
2f9g
Jmol
Contents
Protein chain
332 a.a. *
Ligands
ADP
Metals
_MG
Waters ×102
* Residue conservation analysis
PDB id:
2f9g
Name: Transferase
Title: Crystal structure of fus3 phosphorylated on tyr182
Structure: Mitogen-activated protein kinase fus3. Chain: a. Synonym: map kinase fus3. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: fus3, dac2. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: recombinant fus3 was incubated with an activator peptide from ste5 to achieve full phosphorylation on tyr182 by autophsophorylation.
Resolution:
2.10Å     R-factor:   0.211     R-free:   0.260
Authors: R.P.Bhattacharyya,A.Remenyi,M.C.Good,C.J.Bashor,A.M.Falick, W.A.Lim
Key ref:
R.P.Bhattacharyya et al. (2006). The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway. Science, 311, 822-826. PubMed id: 16424299 DOI: 10.1126/science.1120941
Date:
05-Dec-05     Release date:   14-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P16892  (FUS3_YEAST) -  Mitogen-activated protein kinase FUS3
Seq:
Struc:
353 a.a.
332 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
=
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     periplasmic space   4 terms 
  Biological process     conjugation   13 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.1120941 Science 311:822-826 (2006)
PubMed id: 16424299  
 
 
The Ste5 scaffold allosterically modulates signaling output of the yeast mating pathway.
R.P.Bhattacharyya, A.Reményi, M.C.Good, C.J.Bashor, A.M.Falick, W.A.Lim.
 
  ABSTRACT  
 
Scaffold proteins organize signaling proteins into pathways and are often viewed as passive assembly platforms. We found that the Ste5 scaffold has a more active role in the yeast mating pathway: A fragment of Ste5 allosterically activated autophosphorylation of the mitogen-activated protein kinase Fus3. The resulting form of Fus3 is partially active-it is phosphorylated on only one of two key residues in the activation loop. Unexpectedly, at a systems level, autoactivated Fus3 appears to have a negative regulatory role, promoting Ste5 phosphorylation and a decrease in pathway transcriptional output. Thus, scaffolds not only direct basic pathway connectivity but can precisely tune quantitative pathway input-output properties.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Fus3 recruitment to the pheromone response MAPK complex. (A) Schematic of pheromone response MAPK complex. The MAPK Fus3 interacts with the scaffold protein Ste5 (4–6) and the MAPKK Ste7 (6, 40). (B) Maps of the interaction domains in the MAPKK Ste7 and the scaffold Ste5. Minimal Fus3 binding peptides are shown in color [dark blue, Ste7_pep1 (12, 16); light blue, Ste7_pep2 (16)]. Black bars above the Ste5 schematic indicate protein-interaction domains identified in yeast two-hybrid assays (4, 37). The Fus3 binding peptide (Ste5_pep) is shown in red (fig. S1).
Figure 2.
Fig. 2. Structure of Fus3-Ste5 complex and comparison to canonical docking complexes. (A) Crystal structure of Fus3/Ste5_pep complex. Ste5 (red) binds to Fus3 in a bipartite manner. Close-up views of site A and site B on the right are shown with simulated annealed electron density omit maps (contoured at 1 ) for the Ste5 peptide. (B) Structure of Fus3 in complex with a canonical docking motif from Ste7 (Ste7_pep1) (16). (C) Protein-protein interactions at site A. The N-terminal half of Ste5_pep adopts a ß-strand conformation and initiates the formation of a new ß strand at the N terminus of Fus3 (ß0). This strand forms eight backbone-backbone H bonds with the Fus3 N-terminal region (H bonds are indicated with red dashed lines). The side chain of Q^292 is H bonded to the backbone of ß1, the hydrophobic side chain of I^294 interacts with a groove on the top of the kinase, and Y^295 makes an H bond with the side chain of R^4 from Fus3. Schematic illustration of secondary structural elements of the N-terminal kinase lobe in the unliganded and Ste5_pep liganded complex is shown on the right. (D) Comparison of protein-protein interactions at the canonical MAPK docking groove (site B) between the Fus3/Ste5_pep and the Fus3/Far1_pep complexes (16).
 
  The above figures are reprinted by permission from the AAAs: Science (2006, 311, 822-826) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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PDB code: 3fze
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Dynamic scaffolding in a G protein-coupled signaling system.
  Cell, 131, 80-92.
PDB codes: 2qkt 2qku 2qkv
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Shaping specificity in signaling networks.
  Nat Genet, 39, 286-287.  
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Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae.
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17289571 S.C.Strickfaden, M.J.Winters, G.Ben-Ari, R.E.Lamson, M.Tyers, and P.M.Pryciak (2007).
A mechanism for cell-cycle regulation of MAP kinase signaling in a yeast differentiation pathway.
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A highly conserved MAPK-docking site in Mst7 is essential for Pmk1 activation in Magnaporthe grisea.
  Mol Microbiol, 63, 881-894.  
17715363 X.Zhao, R.Mehrabi, and J.R.Xu (2007).
Mitogen-activated protein kinase pathways and fungal pathogenesis.
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17079133 A.Reményi, M.C.Good, and W.A.Lim (2006).
Docking interactions in protein kinase and phosphatase networks.
  Curr Opin Struct Biol, 16, 676-685.  
16890451 C.J.Caunt, A.R.Finch, K.R.Sedgley, and C.A.McArdle (2006).
Seven-transmembrane receptor signalling and ERK compartmentalization.
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16533805 D.T.Ho, A.J.Bardwell, S.Grewal, C.Iverson, and L.Bardwell (2006).
Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases.
  J Biol Chem, 281, 13169-13179.  
17000758 E.V.Kostenko, O.O.Olabisi, S.Sahay, P.L.Rodriguez, and I.P.Whitehead (2006).
Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs.
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Modular approaches to expanding the functions of living matter.
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Lining the pockets of kinases and phosphatases.
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Protein-protein interactions in the allosteric regulation of protein kinases.
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Docking interactions induce exposure of activation loop in the MAP kinase ERK2.
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PDB code: 2gph
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Networks for the allosteric control of protein kinases.
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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.