Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Three-dimensional structure of a complex between the death domains of Pelle and Tube.

ABSTRACT: The interaction of the serine/threonine kinase Pelle and adaptor protein Tube through their N-terminal death domains leads to the nuclear translocation of the transcription factor Dorsal and activation of zygotic patterning genes during Drosophila embryogenesis. Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold and are arranged in an open-ended linear array with plastic interfaces mediating their interactions. The Tube death domain has an insertion between helices 2 and 3, and a C-terminal tail making significant and indispensable contacts in the heterodimer. In vivo assays of Pelle and Tube mutants confirmed that the integrity of the major heterodimer interface is critical to the activity of these molecules.

SUBMITTER: Xiao T

PROVIDER: S-EPMC4372121 | biostudies-literature | 1999 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Three-dimensional structure of a complex between the death domains of Pelle and Tube.

Xiao T T Towb P P Wasserman S A SA Sprang S R SR

Cell 19991101 5

The interaction of the serine/threonine kinase Pelle and adaptor protein Tube through their N-terminal death domains leads to the nuclear translocation of the transcription factor Dorsal and activation of zygotic patterning genes during Drosophila embryogenesis. Crystal structure of the Pelle and Tube death domain heterodimer reveals that the two death domains adopt a six-helix bundle fold and are arranged in an open-ended linear array with plastic interfaces mediating their interactions. The Tu ...[more]

PMID: 10589682

Similar Datasets

3did: interacting protein domains of known three-dimensional structure.

Project description:The database of 3D Interacting Domains (3did) is a collection of domain-domain interactions in proteins for which high-resolution three-dimensional structures are known. 3did exploits structural information to provide critical molecular details necessary for understanding how interactions occur. It also offers an overview of how similar in structure are interactions between different members of the same protein family. The database also contains Gene Ontology-based functional annotations and interactions between yeast proteins from large-scale interaction discovery studies. A web-based tool to query 3did is available at http://3did.embl.de.

| S-EPMC539991 | biostudies-literature

Pelle Modulates dFoxO-Mediated Cell Death in Drosophila.

Project description:Interleukin-1 receptor-associated kinases (IRAKs) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals. Recent studies also suggest a critical role of IRAKs in tumor development, though the underlying mechanism remains elusive. Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral patterning, innate immune response, muscle development and axon guidance. Here we report a novel function of pll in modulating apoptotic cell death, which is independent of the Toll pathway. We found that loss of pll results in reduced size in wing tissue, which is caused by a reduction in cell number but not cell size. Depletion of pll up-regulates the transcription of pro-apoptotic genes, and triggers caspase activation and cell death. The transcription factor dFoxO is required for loss-of-pll induced cell death. Furthermore, loss of pll activates dFoxO, promotes its translocation from cytoplasm to nucleus, and up-regulates the transcription of its target gene Thor/4E-BP. Finally, Pll physically interacts with dFoxO and phosphorylates dFoxO directly. This study not only identifies a previously unknown physiological function of pll in cell death, but also shed light on the mechanism of IRAKs in cell survival/death during tumorigenesis.

| S-EPMC4608839 | biostudies-literature

Three-dimensional structure and organization of a receptor/signaling complex.

Project description:Transmembrane signaling in bacterial chemotaxis has become an important model system for experimental and theoretical studies. These studies have provided a wealth of detailed molecular structures, including the structures of CheA, CheW, and the cytoplasmic domain of the serine receptor Tsr. How these three proteins interact to form the receptor/signaling complex remains unknown. By using EM and single-particle image analysis, we present a three-dimensional reconstruction of the receptor/signaling complex. The complex contains CheA, CheW, and the cytoplasmic portion of the aspartate receptor Tar. We observe density consistent with a structure containing 24 aspartate-receptor monomers and additional density sufficient to house the expected four CheA monomers and six CheW monomers. Within this bipolar structure are four groups of three receptor dimers that are not threefold symmetric and are therefore unlike the symmetric trimers observed in the x-ray crystal structure of the cytoplasmic domain of the serine receptor. In the latter, the interdimer contacts occur in the signaling domains near the hairpin loop. In our structure, the signaling domains within trimers appear spaced apart by the presence of CheA and CheW. This structure argues against models where one CheA and one CheW bind to the outer face of each of the dimers in the trimer. This structure of the receptor/signaling complex provides an additional basis for understanding the architecture of the large arrays of chemotaxis receptors, CheA, and CheW found at the cell poles in motile bacteria.

| S-EPMC536031 | biostudies-literature

Evidence of complex formation between FADD and c-FLIP death effector domains for the death inducing signaling complex.

Project description:Adaptor protein FADD forms the death inducing signaling complex (DISC) by recruiting the initiating caspases-8 and -10 through homotypic death effector domain (DED) interactions. Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of death ligand-induced apoptosis downstream of death receptors, and FADD competes with procaspase-8/10 for recruitment for DISC. However, the mechanism of action of FADD and c-FLIP proteins remain poorly understood at the molecular level. In this study, we provide evidence indicating that the death effector domain (DED) of FADD interacts directly with the death effector domain of human c-FLIP. In addition, we use homology modeling to develop a molecular docking model of FADD and c-FLIP proteins. We also find that four structure-based mutants (E80A, L84A, K169A and Y171A) of c-FLIP DEDs disturb the interaction with FADD DED, and that these mutations lower the stability of the c-FLIP DED.

| S-EPMC4206723 | biostudies-literature

Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors.

Project description:Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection.

| S-EPMC4364406 | biostudies-literature

Three-dimensional modeling of the human fallopian tube fimbriae.

Project description:Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis.Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5?g/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment.3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome.3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.

| S-EPMC4358821 | biostudies-literature

Three-dimensional EM structure of an intact activator-dependent transcription initiation complex.

Project description:We present the experimentally determined 3D structure of an intact activator-dependent transcription initiation complex comprising the Escherichia coli catabolite activator protein (CAP), RNA polymerase holoenzyme (RNAP), and a DNA fragment containing positions -78 to +20 of a Class I CAP-dependent promoter with a CAP site at position -61.5 and a premelted transcription bubble. A 20-A electron microscopy reconstruction was obtained by iterative projection-based matching of single particles visualized in carbon-sandwich negative stain and was fitted using atomic coordinate sets for CAP, RNAP, and DNA. The structure defines the organization of a Class I CAP-RNAP-promoter complex and supports previously proposed interactions of CAP with RNAP alpha subunit C-terminal domain (alphaCTD), interactions of alphaCTD with sigma(70) region 4, interactions of CAP and RNAP with promoter DNA, and phased-DNA-bend-dependent partial wrapping of DNA around the complex. The structure also reveals the positions and shapes of species-specific domains within the RNAP beta', beta, and sigma(70) subunits.

| S-EPMC2775702 | biostudies-literature

Three-dimensional structure of human chromatin accessibility complex hCHRAC by electron microscopy.

Project description:ATP-dependent chromatin remodeling complexes modulate the dynamic assembly and remodeling of chromatin involved in DNA transcription, replication, and repair. There is little structural detail known about these important multiple-subunit enzymes that catalyze chromatin remodeling processes. Here we report a three-dimensional structure of the human chromatin accessibility complex, hCHRAC, using single particle reconstruction by negative stain electron microscopy. This structure shows an asymmetric 15x10x12nm disk shape with several lobes protruding out of its surfaces. Based on the factors of larger contact area, smaller steric hindrance, and direct involvement of hCHRAC in interactions with the nucleosome, we propose that four lobes on one side form a multiple-site contact surface 10nm in diameter for nucleosome binding. This work provides the first determination of the three-dimensional structure of the ISWI-family of chromatin remodeling complexes.

| S-EPMC2651197 | biostudies-literature

Transistor in a tube: A route to three-dimensional bioelectronics.

Project description:Advances in three-dimensional (3D) cell culture materials and techniques, which more accurately mimic in vivo systems to study biological phenomena, have fostered the development of organ and tissue models. While sophisticated 3D tissues can be generated, technology that can accurately assess the functionality of these complex models in a high-throughput and dynamic manner is not well adapted. Here, we present an organic bioelectronic device based on a conducting polymer scaffold integrated into an electrochemical transistor configuration. This platform supports the dual purpose of enabling 3D cell culture growth and real-time monitoring of the adhesion and growth of cells. We have adapted our system to a 3D tubular geometry facilitating free flow of nutrients, given its relevance in a variety of biological tissues (e.g., vascular, gastrointestinal, and kidney) and processes (e.g., blood flow). This biomimetic transistor in a tube does not require photolithography methods for preparation, allowing facile adaptation to the purpose. We demonstrate that epithelial and fibroblast cells grow readily and form tissue-like architectures within the conducting polymer scaffold that constitutes the channel of the transistor. The process of tissue formation inside the conducting polymer channel gradually modulates the transistor characteristics. Correlating the real-time changes in the steady-state characteristics of the transistor with the growth of the cultured tissue, we extract valuable insights regarding the transients of tissue formation. Our biomimetic platform enabling label-free, dynamic, and in situ measurements illustrates the potential for real-time monitoring of 3D cell culture and compatibility for use in long-term organ-on-chip platforms.

| S-EPMC6203411 | biostudies-literature

Three-dimensional structure of the KdpFABC complex of Escherichia coli by electron tomography of two-dimensional crystals.

Project description:The KdpFABC complex (Kdp) functions as a K+ pump in Escherichia coli and is a member of the family of P-type ATPases. Unlike other family members, Kdp has a unique oligomeric composition and is notable for segregating K+ transport and ATP hydrolysis onto separate subunits (KdpA and KdpB, respectively). We have produced two-dimensional crystals of the KdpFABC complex within reconstituted lipid bilayers and determined its three-dimensional structure from negatively stained samples using a combination of electron tomography and real-space averaging. The resulting map is at a resolution of 2.4 nm and reveals a dimer of Kdp molecules as the asymmetric unit; however, only the cytoplasmic domains are visible due to the lack of stain penetration within the lipid bilayer. The sizes of these cytoplasmic domains are consistent with Kdp and, using a pseudo-atomic model, we have described the subunit interactions that stabilize the Kdp dimer within the larger crystallographic array. These results illustrate the utility of electron tomography in structure determination of ordered assemblies, especially when disorder is severe enough to hamper conventional crystallographic analysis.

| S-EPMC2322856 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data