PDBsum entry: 1yz5

Signaling protein

PDB id: 1yz5

Contents

Protein chains

223 a.a. *

Waters ×72

* Residue conservation analysis

PDB id:

1yz5

Name:

Signaling protein

Title:

The crystal structure of 14-3-3-sigma at 2.8 angstrom resolution

Structure:

14-3-3 protein sigma. Chain: a, b. Synonym: stratifin, epithelial cell marker protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.223 R-free: 0.292

Authors:

A.Benzinger,G.M.Popowicz,T.A.Holak,H.Hermeking

Key ref:

A.Benzinger et al. (2005). The crystal structure of the non-liganded 14-3-3sigma protein: insights into determinants of isoform specific ligand binding and dimerization. Cell Res, 15, 219-227. PubMed id: 15857576 DOI: 10.1038/sj.cr.7290290

Date:

28-Feb-05 Release date: 08-Mar-05

Protein chains

P31947  (1433S_HUMAN) -  14-3-3 protein sigma

Seq: 248 a.a.

Struc: 223 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (4 terms)
• Biological process: cell proliferation (15 terms)
• Biochemical function: protein binding (4 terms)

DOI no: 10.1038/sj.cr.7290290

Cell Res 15:219-227 (2005)

PubMed id: 15857576

The crystal structure of the non-liganded 14-3-3sigma protein: insights into determinants of isoform specific ligand binding and dimerization.

A.Benzinger, G.M.Popowicz, J.K.Joy, S.Majumdar, T.A.Holak, H.Hermeking.

ABSTRACT

Seven different, but highly conserved 14-3-3 proteins are involved in diverse signaling pathways in human cells. It is unclear how the 14-3-3sigma isoform, a transcriptional target of p53, exerts its inhibitory effect on the cell cycle in the presence of other 14-3-3 isoforms, which are constitutively expressed at high levels. In order to identify structural differences between the 14-3-3 isoforms, we solved the crystal structure of the human 14-3-3sigma protein at a resolution of 2.8 Angstroms and compared it to the known structures of 14-3-3zeta and 14-3-3tau. The global architecture of the 14-3-3sigma fold is similar to the previously determined structures of 14-3-3zeta and 14-3-3t: two 14-3-3sigma molecules form a cup-shaped dimer. Significant differences between these 14-3-3 isoforms were detected adjacent to the amphipathic groove, which mediates the binding to phosphorylated consensus motifs in 14-3-3-ligands. Another specificity determining region is localized between amino-acids 203 to 215. These differences presumably select for the interaction with specific ligands, which may explain the different biological functions of the respective 14-3-3 isoforms. Furthermore, the two 14-3-3sigma molecules forming a dimer differ by the spatial position of the ninth helix, which is shifted to the inside of the ligand interaction surface, thus indicating adaptability of this part of the molecule. In addition, 5 non-conserved residues are located at the interface between two 14-3-3sigma proteins forming a dimer and represent candidate determinants of homo- and hetero-dimerization specificity. The structural differences among the 14-3-3 isoforms described here presumably contribute to isoform-specific interactions and functions.

Selected figure(s)

Figure 2.
An overall ribbon plot of the 14-3-3 homodimer. Each monomer consists of nine antiparallel helices and the protein dimerizes in a perfect 2-fold symmetry. The dimer forms a large cup-shaped space between monomers with two phosphopeptide binding sites at its sides. The C-terminal helix of the monomer A (blue) is significantly shifted toward the binding site; chain B is shown in dark-red. (A) a view perpendicular to the helices axis is presented. (B) a view parallel to this axis.

Figure 5.
Ligand recognition by 14-3-3 proteins. (A) Unbound (red) and (blue) are superimposed with the structure of the isoform (green) bound to serotonin N-acetyltransferase (C trace) to indicate the structural diversity of the Ala203 and Asp215 loop area. (B) Structures of (blue) and (red) are overlaid. The molecular surface of the isoform is shown half-transparent. The structure and surface of the phosphopeptide from the 1QJA model is shown in light blue. Non-conserved residues in this area are labeled for the isoform. Significant difference in the Ala203 and Asp215 loop are evident.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Cell Res (2005, 15, 219-227) copyright 2005.

Figures were selected by an automated process.