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

Benzinger, Anne; Popowicz, Grzegorz M.; Joy, Joma; Majumdar, Sudipta; Holak, Tad A.; Hermeking, Heiko

doi:10.1038/sj.cr.7290290

Cited by 102 publications

(88 citation statements)

References 29 publications

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“…Comparative structural analyses of 14-3-3 isoforms suggested regions, including the surface formed by helices H8 and H9 (Fig. 3C), which presumably dictate ligand and dimerization preferences (44,55,56). Our results show that the RGS domain of RGS3 interacts with the less conserved regions of helices H6 and H8 outside the central channel of the 14-3-3 dimer (Figs.…”

Section: Discussionmentioning

confidence: 57%

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Structural Basis for the 14-3-3 Protein-dependent Inhibition of the Regulator of G Protein Signaling 3 (RGS3) Function

Rezabkova

Man

Novák

et al. 2011

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 57%

“…Residues that are totally conserved among all human isoforms are colored in yellow. The black ellipses in panels B and C indicate the specificity region believed to be involved in protein-protein interactions and responsible for isoform-selective contacts (44,55,56).…”

Section: Biophysical Characterization Of the 14-3-3⅐prgs3 Proteinmentioning

confidence: 99%

Structural Basis for the 14-3-3 Protein-dependent Inhibition of the Regulator of G Protein Signaling 3 (RGS3) Function

Rezabkova

Man

Novák

et al. 2011

Journal of Biological Chemistry

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“…It is important in the future to analyze the ligand specificity and promoter regulation of 14-3-3 ⑀, , and ␥ to determine how these factors may affect 14-3-3 family member specificity during embryogenesis. Other studies have shown that the C-terminus of 14-3-3 proteins mediate family member-specific ligand interactions (Benzinger et al, 2005;Bornke, 2005). Our alignment of the X. laevis 14-3-3 protein sequences showed little amino acid variability in the Cterminus, with the exception of 14-3-3 ⑀, which is unique among the six family members in having an additional sequence of negatively charged amino acid residues (Fig.…”

Section: Discussionmentioning

confidence: 95%

Differential role of 14‐3‐3 family members in Xenopus development

Lau

Muslin

2006

Developmental Dynamics

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The 14-3-3 proteins are intracellular dimeric phosphoserine/threonine binding molecules that participate in signal transduction, checkpoint control, nutrient sensing, and cell survival pathways. Previous work established that 14-3-3 proteins are required in early Xenopus laevis development by modulating fibroblast growth factor signaling. Although this general requirement for 14-3-3 proteins in Xenopus early embryogenesis is established, there is no information about the specific role of individual 14-3-3 genes. Botanical studies previously demonstrated functional specificity among 14-3-3 genes during plant development. In this study, an antisense morpholino oligo microinjection approach was used to characterize the requirement for six specific 14-3-3 family members in Xenopus embryogenesis. Microinjection experiments followed by Western blot analysis showed that morpholinos reduced specific 14-3-3 protein levels. Embryos lacking specific 14-3-3 isoforms displayed unique phenotypic defects. In particular, reduction of 14-3-3 tau () protein, and to a lesser extent, 14-3-3 epsilon (⑀), resulted in embryos with prominent gastrulation and axial patterning defects and reduced mesodermal marker gene expression. In contrast, reduction of 14-3-3 zeta () protein caused no obvious phenotypic abnormalities. Reduction of 14-3-3 gamma (␥) protein resulted in eye defects without gastrulation abnormalities. Therefore, individual 14-3-3 genes have separable functions in vertebrate embryonic development.

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“…No low-desolvation patches were observed for any of the isoforms in the conserved peptide binding groove or on the opposite face of each monomer. Two major ODA sites occur consistently for all 14-3-3 family members: site S1, located at the observed dimerization interface, and site S2 in the solvent accessible side of the helices ␣H and ␣I, located close to the previously identified specificity region (37).…”

Section: Resultsmentioning

confidence: 99%

“…Previously, a number of three-dimensional structures of 14-3-3 isoforms have been determined and deposited in the Protein Data Bank (PDB; www.pdb.org): , in its apo form (35), as peptide complexes (14,17,18) and in complex with serotonin N-acetyltransferase (AANAT) (36); and in apo-and peptide-bound states (37,38). In addition, the structure of was published (39) but not deposited in the PDB.…”

mentioning

confidence: 99%

Structural basis for protein–protein interactions in the 14-3-3 protein family

Yang

Lee

Sobott

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

342

419

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The seven members of the human 14-3-3 protein family regulate a diverse range of cell signaling pathways by formation of proteinprotein complexes with signaling proteins that contain phosphorylated Ser͞Thr 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.phosphorylation ͉ signaling

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

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-

Cited by 102 publications

References 29 publications

Structural Basis for the 14-3-3 Protein-dependent Inhibition of the Regulator of G Protein Signaling 3 (RGS3) Function

Structural Basis for the 14-3-3 Protein-dependent Inhibition of the Regulator of G Protein Signaling 3 (RGS3) Function

Differential role of 14‐3‐3 family members in Xenopus development

Structural basis for protein–protein interactions in the 14-3-3 protein family

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