Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An updated view on the structure and function of PYRIN domains.

ABSTRACT: The PYRIN domain (PYD) is a protein-protein interaction domain, which belongs to the death domain fold (DDF) superfamily. It is best known for its signaling function in innate immune responses and particularly in the assembly of inflammasomes, which are large protein complexes that allow the induced proximity-mediated activation of caspase-1 and subsequently the release of pro-inflammatory cytokines. The molecular mechanism of inflammasome assembly was only recently elucidated and specifically requires PYD oligomerization. Here we discuss the recent advances in our understanding of PYD signaling and its regulation by PYD-only proteins.

SUBMITTER: Chu LH

PROVIDER: S-EPMC4297229 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An updated view on the structure and function of PYRIN domains.

Chu Lan Hoang LH Gangopadhyay Anu A Dorfleutner Andrea A Stehlik Christian C

Apoptosis : an international journal on programmed cell death 20150201 2

The PYRIN domain (PYD) is a protein-protein interaction domain, which belongs to the death domain fold (DDF) superfamily. It is best known for its signaling function in innate immune responses and particularly in the assembly of inflammasomes, which are large protein complexes that allow the induced proximity-mediated activation of caspase-1 and subsequently the release of pro-inflammatory cytokines. The molecular mechanism of inflammasome assembly was only recently elucidated and specifically r ...[more]

PMID: 25451010

Similar Datasets

Plant HKT Channels: An Updated View on Structure, Function and Gene Regulation.

Project description:HKT channels are a plant protein family involved in sodium (Na+) and potassium (K+) uptake and Na+-K+ homeostasis. Some HKTs underlie salt tolerance responses in plants, while others provide a mechanism to cope with short-term K+ shortage by allowing increased Na+ uptake under K+ starvation conditions. HKT channels present a functionally versatile family divided into two classes, mainly based on a sequence polymorphism found in the sequences underlying the selectivity filter of the first pore loop. Physiologically, most class I members function as sodium uniporters, and class II members as Na+/K+ symporters. Nevertheless, even within these two classes, there is a high functional diversity that, to date, cannot be explained at the molecular level. The high complexity is also reflected at the regulatory level. HKT expression is modulated at the level of transcription, translation, and functionality of the protein. Here, we summarize and discuss the structure and conservation of the HKT channel family from algae to angiosperms. We also outline the latest findings on gene expression and the regulation of HKT channels.

| S-EPMC7918770 | biostudies-literature

Identification of multifaceted binding modes for pyrin and ASC pyrin domains gives insights into pyrin inflammasome assembly.

Project description:Inflammasomes are macromolecular complexes that mediate inflammatory and cell death responses to pathogens and cellular stress signals. Dysregulated inflammasome activation is associated with autoinflammatory syndromes and several common diseases. During inflammasome assembly, oligomerized cytosolic pattern recognition receptors recruit procaspase-1 and procaspase-8 via the adaptor protein ASC. Inflammasome assembly is mediated by pyrin domains (PYDs) and caspase recruitment domains, which are protein interaction domains of the death fold superfamily. However, the molecular details of their interactions are poorly understood. We have studied the interaction between ASC and pyrin PYDs that mediates ASC recruitment to the pyrin inflammasome, which is implicated in the pathogenesis of familial Mediterranean fever. We demonstrate that both the ASC and pyrin PYDs have multifaceted binding modes, involving three sites on pyrin PYD and two sites on ASC PYD. Molecular docking of pyrin-ASC PYD complexes showed that pyrin PYD can simultaneously interact with up to three ASC PYDs. Furthermore, ASC PYD can self-associate and interact with pyrin, consistent with previous reports that pyrin promotes ASC clustering to form a proinflammatory complex. Finally, the effects of familial Mediterranean fever-associated mutations, R42W and A89T, on structural and functional properties of pyrin PYD were investigated. The R42W mutation had a significant effect on structure and increased stability. Although the R42W mutant exhibited reduced interaction with ASC, it also bound less to the pyrin B-box domain responsible for autoinhibition and hence may be constitutively active. Our data give new insights into the binding modes of PYDs and inflammasome architecture.

| S-EPMC4156052 | biostudies-literature

Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity.

Project description:The innate immune system provides an initial line of defense against infection. Nucleotide-binding domain- and leucine-rich repeat-containing protein (NLR or (NOD-like)) receptors play a critical role in the innate immune response by surveying the cytoplasm for traces of intracellular invaders and endogenous stress signals. NLRs themselves are multi-domain proteins. Their N-terminal effector domains (typically a pyrin or caspase activation and recruitment domain) are responsible for driving downstream signaling and initiating the formation of inflammasomes, multi-component complexes necessary for cytokine activation. However, the currently available structures of NLR effector domains have not yet revealed the mechanism of their differential modes of interaction. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD) obtained by NMR spectroscopy. The NLRP7 PYD adopts a six-alpha-helix bundle death domain fold. A comparison of conformational and dynamics features of the NLRP7 PYD with other PYDs showed distinct differences for helix alpha3 and loop alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster. Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This is significant, because death domain signaling is driven by electrostatic contacts and stabilized by hydrophobic interactions. Thus, these results provide new insights into NLRP signaling and provide a first molecular understanding of inflammasome formation.

| S-EPMC2930738 | biostudies-literature

Troponin structure and function: a view of recent progress.

Project description:The molecular mechanism by which Ca2+ binding and phosphorylation regulate muscle contraction through Troponin is not yet fully understood. Revealing the differences between the relaxed and active structure of cTn, as well as the conformational changes that follow phosphorylation has remained a challenge for structural biologists over the years. Here we review the current understanding of how Ca2+, phosphorylation and disease-causing mutations affect the structure and dynamics of troponin to regulate the thin filament based on electron microscopy, X-ray diffraction, NMR and molecular dynamics methodologies.

| S-EPMC7109197 | biostudies-literature

Enzymes: An integrated view of structure, dynamics and function.

Project description:Microbes utilize enzymes to perform a variety of functions. Enzymes are biocatalysts working as highly efficient machines at the molecular level. In the past, enzymes have been viewed as static entities and their function has been explained on the basis of direct structural interactions between the enzyme and the substrate. A variety of experimental and computational techniques, however, continue to reveal that proteins are dynamically active machines, with various parts exhibiting internal motions at a wide range of time-scales. Increasing evidence also indicates that these internal protein motions play a role in promoting protein function such as enzyme catalysis. Moreover, the thermodynamical fluctuations of the solvent, surrounding the protein, have an impact on internal protein motions and, therefore, on enzyme function. In this review, we describe recent biochemical and theoretical investigations of internal protein dynamics linked to enzyme catalysis. In the enzyme cyclophilin A, investigations have lead to the discovery of a network of protein vibrations promoting catalysis. Cyclophilin A catalyzes peptidyl-prolyl cis/trans isomerization in a variety of peptide and protein substrates. Recent studies of cyclophilin A are discussed in detail and other enzymes (dihydrofolate reductase and liver alcohol dehydrogenase) where similar discoveries have been reported are also briefly discussed. The detailed characterization of the discovered networks indicates that protein dynamics plays a role in rate-enhancement achieved by enzymes. An integrated view of enzyme structure, dynamics and function have wide implications in understanding allosteric and co-operative effects, as well as protein engineering of more efficient enzymes and novel drug design.

| S-EPMC1379655 | biostudies-literature

Structure and function of HCV IRES domains.

Project description:The HCV IRES is a highly structured RNA which mediates cap-independent translation initiation in higher eukaryotes. This function is encoded in conserved structural motifs in the two major domains of HCV and HCV-like IRESs, which play crucial and distinct roles along the initiation pathway. In this review, I discuss structural features of IRES domains and how these RNA motifs function as RNA-based initiation factors to form 48S initiation complexes and 80S ribosomes with only a subset of canonical, protein-based eukaryotic initiation factors.

| S-EPMC2726286 | biostudies-literature

A global view of structure-function relationships in the tautomerase superfamily.

Project description:The tautomerase superfamily (TSF) consists of more than 11,000 nonredundant sequences present throughout the biosphere. Characterized members have attracted much attention because of the unusual and key catalytic role of an N-terminal proline. These few characterized members catalyze a diverse range of chemical reactions, but the full scale of their chemical capabilities and biological functions remains unknown. To gain new insight into TSF structure-function relationships, we performed a global analysis of similarities across the entire superfamily and computed a sequence similarity network to guide classification into distinct subgroups. Our results indicate that TSF members are found in all domains of life, with most being present in bacteria. The eukaryotic members of the cis-3-chloroacrylic acid dehalogenase subgroup are limited to fungal species, whereas the macrophage migration inhibitory factor subgroup has wide eukaryotic representation (including mammals). Unexpectedly, we found that 346 TSF sequences lack Pro-1, of which 85% are present in the malonate semialdehyde decarboxylase subgroup. The computed network also enabled the identification of similarity paths, namely sequences that link functionally diverse subgroups and exhibit transitional structural features that may help explain reaction divergence. A structure-guided comparison of these linker proteins identified conserved transitions between them, and kinetic analysis paralleled these observations. Phylogenetic reconstruction of the linker set was consistent with these findings. Our results also suggest that contemporary TSF members may have evolved from a short 4-oxalocrotonate tautomerase-like ancestor followed by gene duplication and fusion. Our new linker-guided strategy can be used to enrich the discovery of sequence/structure/function transitions in other enzyme superfamilies.

| S-EPMC5818174 | biostudies-literature

The NLRP12 pyrin domain: structure, dynamics, and functional insights.

Project description:The initial line of defense against infection is sustained by the innate immune system. Together, membrane-bound Toll-like receptors and cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLR) play key roles in the innate immune response by detecting bacterial and viral invaders as well as endogenous stress signals. NLRs are multi-domain proteins with varying N-terminal effector domains that are responsible for regulating downstream signaling events. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP12 (NLRP12 PYD) determined using NMR spectroscopy. NLRP12 is a non-inflammasome NLR that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-κB activation. NLRP12 PYD adopts a typical six-helical bundle death domain fold. By direct comparison with other PYD structures, we identified hydrophobic residues that are essential for the stable fold of the NLRP PYD family. In addition, we report the first in vitro confirmed non-homotypic PYD interaction between NLRP12 PYD and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling. Interestingly, all residues that participate in this protein:protein interaction are confined to the α2-α3 surface, a region of NLRP12 PYD that differs most between currently reported NLRP PYD structures. Finally, we experimentally highlight a significant role for tryptophan 45 in the interaction between NLRP12 PYD and the FAF-1 UBA domain.

| S-EPMC3202057 | biostudies-literature

Dynamic New World: Refining Our View of Protein Structure, Function and Evolution.

Project description:Proteins are crucial to the functioning of all lifeforms. Traditional understanding posits that a single protein occupies a single structure ("fold"), which performs a single function. This view is radically challenged with the recognition that high structural dynamism-the capacity to be extra "floppy"-is more prevalent in functional proteins than previously assumed. As reviewed here, this dynamic take on proteins affects our understanding of protein "structure", function, and evolution, and even gives us a glimpse into protein origination. Specifically, this review will discuss historical developments concerning protein structure, and important new relationships between dynamism and aspects of protein sequence, structure, binding modes, binding promiscuity, evolvability, and origination. Along the way, suggestions will be provided for how key parts of textbook definitions-that so far have excluded membership to intrinsically disordered proteins (IDPs)-could be modified to accommodate our more dynamic understanding of proteins.

| S-EPMC5302727 | biostudies-literature

Fusing structure and function: a structural view of the herpesvirus entry machinery.

Project description:Herpesviruses are double-stranded DNA, enveloped viruses that infect host cells through fusion with either the host cell plasma membrane or endocytic vesicle membranes. Efficient infection of host cells by herpesviruses is remarkably more complex than infection by other viruses, as it requires the concerted effort of multiple glycoproteins and involves multiple host receptors. The structures of the major viral glycoproteins and a number of host receptors involved in the entry of the prototypical herpesviruses, the herpes simplex viruses (HSVs) and Epstein-Barr virus (EBV), are now known. These structural studies have accelerated our understanding of HSV and EBV binding and fusion by revealing the conformational changes that occur on virus-receptor binding, depicting potential sites of functional protein and lipid interactions, and identifying the probable viral fusogen.

| S-EPMC3242325 | 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