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PDBsum entry 2btp

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protein ligands Protein-protein interface(s) links
Signaling protein/peptide PDB id
2btp
Jmol
Contents
Protein chains
248 a.a. *
221 a.a. *
Ligands
ARG-GLN-ARG-SEP-
ALA-PRO
×2
* Residue conservation analysis
PDB id:
2btp
Name: Signaling protein/peptide
Title: 14-3-3 protein theta (human) complexed to peptide
Structure: 14-3-3 protein tau. Chain: a, b. Synonym: 14-3-3 protein theta, 14-3-3 protein t-cell, hs1 protein. Engineered: yes. Consensus peptide for 14-3-3 proteins. Chain: p, q. Other_details: phosphoserine at residues p 5 and q 5
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: bl21(de3). Other_details: the mammalian gene collection, i.M.A.G.E. Consortium cloneid 6164592. Synthetic: yes.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.210     R-free:   0.259
Authors: J.M.Elkins,A.C.E.Johansson,C.Smee,X.Yang,M.Sundstrom, A.Edwards,C.Arrowsmith,D.A.Doyle, Structural Genomics Consortium
Key ref:
X.Yang et al. (2006). Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc Natl Acad Sci U S A, 103, 17237-17242. PubMed id: 17085597 DOI: 10.1073/pnas.0605779103
Date:
05-Jun-05     Release date:   28-Jun-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P27348  (1433T_HUMAN) -  14-3-3 protein theta
Seq:
Struc:
245 a.a.
248 a.a.
Protein chain
Pfam   ArchSchema ?
P27348  (1433T_HUMAN) -  14-3-3 protein theta
Seq:
Struc:
245 a.a.
221 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     membrane organization   8 terms 
  Biochemical function     protein binding     3 terms  

 

 
DOI no: 10.1073/pnas.0605779103 Proc Natl Acad Sci U S A 103:17237-17242 (2006)
PubMed id: 17085597  
 
 
Structural basis for protein-protein interactions in the 14-3-3 protein family.
X.Yang, W.H.Lee, F.Sobott, E.Papagrigoriou, C.V.Robinson, J.G.Grossmann, M.Sundström, D.A.Doyle, J.M.Elkins.
 
  ABSTRACT  
 
The seven members of the human 14-3-3 protein family regulate a diverse range of cell signaling pathways by formation of protein-protein complexes with signaling proteins that contain phosphorylated Ser/Thr residues within specific sequence motifs. Previously, crystal structures of three 14-3-3 isoforms (zeta, sigma, and tau) have been reported, with structural data for two isoforms deposited in the Protein Data Bank (zeta and sigma). In this study, we provide structural detail for five 14-3-3 isoforms bound to ligands, providing structural coverage for all isoforms of a human protein family. A comparative structural analysis of the seven 14-3-3 proteins revealed specificity determinants for binding of phosphopeptides in a specific orientation, target domain interaction surfaces and flexible adaptation of 14-3-3 proteins through domain movements. Specifically, the structures of the beta isoform in its apo and peptide bound forms showed that its binding site can exhibit structural flexibility to facilitate binding of its protein and peptide partners. In addition, the complex of 14-3-3 beta with the exoenzyme S peptide displayed a secondary structural element in the 14-3-3 peptide binding groove. These results show that the 14-3-3 proteins are adaptable structures in which internal flexibility is likely to facilitate recognition and binding of their interaction partners.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Schematic representation of the heterodimerization process involving the (green) and (yellow) isoforms. The lines between identified residues indicate specific interactions.
Figure 5.
Fig. 5. Dynamic nature of the 14-3-3 dimers. (A) Crystal structure of the apo- isoform looking down the peptide binding grooves, which are labeled open and closed for the individual monomers. (B) Superimposition of all seven closed state 14-3-3 isoforms using only one monomer as the reference, with shown in blue and in green. The other 14-3-3 monomers, which have intermediate positions, are colored transparent gray.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420405 H.J.Bustad, J.Underhaug, O.Halskau, and A.Martinez (2011).
The binding of 14-3-3γ to membranes studied by intrinsic fluorescence spectroscopy.
  FEBS Lett, 585, 1163-1168.  
21182262 S.Mokhtarzada, C.Yu, A.Brickenden, and W.Y.Choy (2011).
Structural characterization of partially disordered human chibby: insights into its function in the wnt-signaling pathway.
  Biochemistry, 50, 715-726.  
20141511 C.Johnson, S.Crowther, M.J.Stafford, D.G.Campbell, R.Toth, and C.MacKintosh (2010).
Bioinformatic and experimental survey of 14-3-3-binding sites.
  Biochem J, 427, 69-78.  
19920133 G.Messaritou, S.Grammenoudi, and E.M.Skoulakis (2010).
Dimerization is essential for 14-3-3zeta stability and function in vivo.
  J Biol Chem, 285, 1692-1700.  
20483341 H.Toncrova, and T.C.McLeish (2010).
Substrate-modulated thermal fluctuations affect long-range allosteric signaling in protein homodimers: exemplified in CAP.
  Biophys J, 98, 2317-2326.  
20007511 M.Agassandian, B.B.Chen, C.C.Schuster, J.C.Houtman, and R.K.Mallampalli (2010).
14-3-3zeta escorts CCTalpha for calcium-activated nuclear import in lung epithelia.
  FASEB J, 24, 1271-1283.  
19933256 S.Rajagopalan, R.S.Sade, F.M.Townsley, and A.R.Fersht (2010).
Mechanistic differences in the transcriptional activation of p53 by 14-3-3 isoforms.
  Nucleic Acids Res, 38, 893-906.  
20166753 S.Vega-Rubin-de-Celis, Z.Abdallah, L.Kinch, N.V.Grishin, J.Brugarolas, and X.Zhang (2010).
Structural analysis and functional implications of the negative mTORC1 regulator REDD1.
  Biochemistry, 49, 2491-2501.
PDB code: 3lq9
19489729 A.Edwards (2009).
Large-scale structural biology of the human proteome.
  Annu Rev Biochem, 78, 541-568.  
19608861 C.Choudhary, C.Kumar, F.Gnad, M.L.Nielsen, M.Rehman, T.C.Walther, J.V.Olsen, and M.Mann (2009).
Lysine acetylation targets protein complexes and co-regulates major cellular functions.
  Science, 325, 834-840.  
19531356 L.K.Nutt, M.R.Buchakjian, E.Gan, R.Darbandi, S.Y.Yoon, J.Q.Wu, Y.J.Miyamoto, J.A.Gibbons, J.A.Gibbon, J.L.Andersen, C.D.Freel, W.Tang, C.He, M.Kurokawa, Y.Wang, S.S.Margolis, R.A.Fissore, and S.Kornbluth (2009).
Metabolic control of oocyte apoptosis mediated by 14-3-3zeta-regulated dephosphorylation of caspase-2.
  Dev Cell, 16, 856-866.  
17972165 T.Wang, L.Xue, X.Ji, J.Li, Y.Wang, and Y.Feng (2009).
Cloning and characterization of the 14-3-3 protein gene from the halotolerant alga Dunaliella salina.
  Mol Biol Rep, 36, 207-214.  
  19956445 Z.Li, J.Y.Liu, and J.T.Zhang (2009).
14-3-3sigma, the double-edged sword of human cancers.
  Am J Transl Res, 1, 326-340.  
19801645 ..Halskau, M.Ying, A.Baumann, R.Kleppe, D.Rodriguez-Larrea, B.Almås, J.Haavik, and A.Martinez (2009).
Three-way interaction between 14-3-3 proteins, the N-terminal region of tyrosine hydroxylase, and negatively charged membranes.
  J Biol Chem, 284, 32758-32769.  
18250626 A.Edwards (2008).
Bermuda Principles meet structural biology.
  Nat Struct Mol Biol, 15, 116.  
19001422 S.Visconti, L.Camoni, M.Marra, and P.Aducci (2008).
Role of the 14-3-3 C-terminal region in the interaction with the plasma membrane H+-ATPase.
  Plant Cell Physiol, 49, 1887-1897.  
17932789 O.Gileadi, S.Knapp, W.H.Lee, B.D.Marsden, S.Müller, F.H.Niesen, K.L.Kavanagh, L.J.Ball, F.von Delft, D.A.Doyle, U.C.Oppermann, and M.Sundström (2007).
The scientific impact of the Structural Genomics Consortium: a protein family and ligand-centered approach to medically-relevant human proteins.
  J Struct Funct Genomics, 8, 107-119.  
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.