Crystal Structure of the 14-3-3ζ:Serotonin N-Acetyltransferase Complex

Obšil, Tomáš; Ghirlando, Rodolfo; Klein, David C.; Ganguly, Shantanu; Dyda, Fred

doi:10.1016/s0092-8674(01)00316-6

Cited by 360 publications

(391 citation statements)

References 46 publications

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“…The two additional structures of 14-3-3ζ and 14-3-3τ were determined bound to a phosphopeptide or a sulfate group, respectively. In addition, the structure of 14-3-3ζ has the same overall fold compared to the published structures of the ζ and τ isoforms [15]. The structure of 14-3-3σ has the same overall fold as the known fold of the ζ and τ isoforms (Fig.…”

Section: Resultsmentioning

confidence: 58%

“…Structural comparison of 14-3-3σ σ σ σ σ, τ τ τ τ τ and ζ ζ ζ ζ ζ We compared our structure of 14-3-3σ to the previously published structures of 14-3-3ζ and 14-3-3τ [12,15,22,23]. Only the structure of 14-3-3ζ solved by Liu et al was determined in an unliganded form, i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Association with 14-3-3 proteins regulates the function of ligands by inter-and intra-compartmental sequestration, activation/inactivation of enzymatic activity and promotion/inhibition of protein-interactions; thereby, numerous cellular processes in all multi-cellular species analyzed are regulated by 14-3-3 proteins (reviewed in [1,13,14]). In part this regulation is mediated by conformational changes of the ligand after association with 14-3-3 proteins [15].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2005

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Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

et al. 2005

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“…A recent study involving cocrystallization of 14-3-3 with the enzyme serotonin N-acetyltransferase (AANAT) provides a more comprehensive understanding of the 14-3-3-target structure (Obsil et al, 2001). As the only existing example of a structure of 14-3-3 bound to a target protein, this study provides a somewhat different picture than that derived from studies with short peptides; full-length AANAT, which contains two potential 14-3-3 binding sites (e.g., T31 and S205), forms exclusively 1:2 stoichiometric complexes with 14-3-3 in vitro, suggesting that a dimeric 14-3-3 binds to a single AANAT polypeptide at two sites.…”

Section: Discussionmentioning

confidence: 99%

Significance of 14-3-3 Self-Dimerization for Phosphorylation-dependent Target Binding

Shen

Godlewski

Bronisz

et al. 2003

MBoC

105

117

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14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed against a degenerated mode-1 14-3-3 binding motif (RSxpSxP), we demonstrate that most of the 14-3-3-associated proteins in COS-7 cells are phosphorylated on sites that react with this antibody. The binding of these phosphoproteins depends on 14-3-3 dimerization, inasmuch as proteins associated in vivo with a monomeric 14-3-3 form are not recognized by the phospho-specific antibody. The role of 14-3-3 dimerization in the phosphorylation-dependent target binding is further exemplified with two well-defined 14-3-3 targets, Raf and DAF-16. Raf and DAF-16 can bind both monomeric and dimeric 14-3-3; however, whereas phosphorylation of specific Raf and DAF-16 sites is required for binding to dimeric 14-3-3, binding to monomeric 14-3-3 forms is entirely independent of Raf and DAF-16 phosphorylation. We also find that dimerization diminishes 14-3-3 susceptibility to phosphorylation. These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other

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“…This protein family can either positively modulate enzyme activity, in the cases of serotonin Nacetyltransferase (Obsil et al 2001) and Protein Kinase C (Van Der Hoeven et al 2000), or negatively modulate activity, such as with CaM-kinase kinase (Davare et al 2004). Specifically in the ERK pathways, 14-3-3 does not impact the activity of MEK (Shimizu et al 1994), but it has been reported to stimulate the enzyme upstream from MEK, Raf (Freed et al 1994) ) and associates with other upstream kinases in the pathway (Yamamori et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Differential activation of extracellular signal-regulated kinase 1 and a related complex in neuronal nuclei

Lundquist

Dudek

2006

Brain Cell Bio

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The Extracellular signal-Regulated Kinases 1 and 2 (ERKs 1/2) are known to participate in regulating transcription in response to moderate depolarization (synaptic stimulation), but how the same active enzyme can differentially regulate distinct transcriptional programs induced with abnormal depolarization (high potassium) is unknown. We hypothesized that ERK1 or 2 accomplishes this differential nuclear response through close association with other proteins in stable complexes. In support of this hypothesis, we have found that immunoreactivity for an apparent high molecular weight phospho-ERK1-containing complex increased in response to synaptic stimulation, but decreased in response to high potassium; p-ERK immunoreactivity at 44/42 kDa increased in both cases. Evidence supporting the conclusion that the band of interest contained ERK1 in a complex, as opposed to it being an unrelated protein crossreacting with antibodies against p-ERK, is that ERK1 (p44 MAPK) and 14-3-3 were electro-eluted from the 160 kDa band cut from a gel. We also found the nuclear complexes to be exceptionally durable, suggesting a role for the crosslinking enzyme, transglutaminase, in its stabilization. In addition, we found other components of the ERK pathway, including MEK, ERK2, p90RSK, and Elk-1, migrating at higher-than-expected weights in brain nuclei. These results describe a novel stable complex of ERK1 in neuronal nuclei that responds differentially to synaptic and depolarizing stimulation, and thus may be capable of mediating gene transcription in a way distinct from the monomeric protein.

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Crystal Structure of the 14-3-3ζ:Serotonin N-Acetyltransferase Complex

Cited by 360 publications

References 46 publications

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

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

Significance of 14-3-3 Self-Dimerization for Phosphorylation-dependent Target Binding

Differential activation of extracellular signal-regulated kinase 1 and a related complex in neuronal nuclei

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