Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Conformational dynamics of actin: effectors and implications for biological function.

ABSTRACT: Actin is a protein abundant in many cell types. Decades of investigations have provided evidence that it has many functions in living cells. The diverse morphology and dynamics of actin structures adapted to versatile cellular functions is established by a large repertoire of actin-binding proteins. The proper interactions with these proteins assume effective molecular adaptations from actin, in which its conformational transitions play essential role. This review attempts to summarise our current knowledge regarding the coupling between the conformational states of actin and its biological function.

SUBMITTER: Hild G

PROVIDER: S-EPMC3038201 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Conformational dynamics of actin: effectors and implications for biological function.

Hild Gábor G Bugyi Beáta B Nyitrai Miklós M

Cytoskeleton (Hoboken, N.J.) 20101001 10

Actin is a protein abundant in many cell types. Decades of investigations have provided evidence that it has many functions in living cells. The diverse morphology and dynamics of actin structures adapted to versatile cellular functions is established by a large repertoire of actin-binding proteins. The proper interactions with these proteins assume effective molecular adaptations from actin, in which its conformational transitions play essential role. This review attempts to summarise our curre ...[more]

PMID: 20672362

Similar Datasets

Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery.

Project description:Nuclear receptors are targets for a wide range of ligands, both natural and synthetic, that regulate their activity and provide a means to pharmacologically modulate the receptor. Recent emphasis in the nuclear receptor field has focused on selective nuclear receptor modulators, which can display graded transcriptional responses and tissue selective pharmacological responses that deviate from the prototypical agonist or antagonist. Understanding the molecular mechanism of action of these selective modulators will provide significant insight toward the development of the next generation of modulators. Although most nuclear receptor structural studies have primarily focused on obtaining ligand-receptor cocrystal structures, recent studies implicate an important role for protein dynamics in the mechanism of action of nuclear receptor ligands. Here we review nuclear receptor studies reporting how ligands modulate the conformational dynamics of the nuclear receptor ligand-binding domain (LBD). A particular emphasis is placed on protein NMR and hydrogen/deuterium exchange (HDX) techniques and how they provide complementary information that, when combined with crystallography, provide detailed insight into the function of nuclear receptors.

| S-EPMC3533479 | biostudies-literature

Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens.

Project description:Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway.

| S-EPMC2610399 | biostudies-literature

Conformational Dynamics of Deubiquitinase A and Functional Implications.

Project description:Deubiquitinase A (DUBA) belongs to the ovarian tumor family of deubiquitinating enzymes and was initially identified as a negative regulator of type I interferons, whose overproduction has been linked to autoimmune diseases. The deubiquitinating activity of DUBA is positively regulated by phosphorylation at a single serine residue, S177, which results in minimal structural changes. We have previously shown that phosphorylation induces a two-state conformational equilibrium observed only in the active form of DUBA, highlighting the functional importance of DUBA dynamics. Here, we report the conformational dynamics of DUBA on the microsecond-to-millisecond time scales characterized by nuclear magnetic resonance relaxation dispersion experiments. We found that motions on these time scales are highly synchronized in the phosphorylated and nonphosphorylated DUBA. Despite the overall similarity of these two forms, different dynamic properties were observed in helix α1 and the neighboring regions, including residue S177, which likely contribute to the activation of DUBA by phosphorylation. Moreover, our data suggest that transient unfolding of helix α6 drives the global conformational process and that mutations can be introduced to modulate this process, which provides a basis for future studies to define the exact functional roles of motions in DUBA activation and substrate specificity.

| S-EPMC7872723 | biostudies-literature

Reconstructing de novo silencing of an active plant retrotransposon: dynamics, mechanisms, biological implications

Project description:In plants, maintenance-methylation mediated by METHYLTRANSFERASE-1 (MET1), siRNA-directed de-novo methylation, and chromatin remodeling by DECREASE IN DNA METHYLATION -1 (DDM1) promote transcriptional gene-silencing of transposable elements (TEs). This process is mostly investigated at steady states reflecting how long-established silent conditions are maintained, faithfully re-iterated or temporarily modified during growth, stress and over generations. How invasive TEs are detected and silenced de novo, however, remains largely unknown. Using inbred lineages of hybrid Arabidopsis epigenomes combining wild-type and met1 or ddm1 chromosomes, we have deciphered the timing, spatial distribution and mechanisms underpinning the proliferation and eventual demise of the endogenous retrotransposon évadé (EVD). Both developmental and molecular features of EVD biology, including a remarkable ability to evade RNA interference, ultimately contribute to its silencing over multiple generations. The underlying processes are accompanied by widespread diversification of the Arabidopsis genome and de-novo epiallelism creating an extensive reservoir of selectable and potentially adaptive traits. Differential expression of EVADE small RNAs between three generations of one specific Col0 met1 derived EpiRIL.

2013-07-02 | E-GEOD-43412 | biostudies-arrayexpress

Role of Cofilin 1 pathway and actin dynamics in nuclear retinoid receptor function

Project description:We have investigated the role of actin dynamics and the effect of actin cytoskeleton modifying agents on retinoid receptor-mediated transactivation. Using Nef, an actin modifying HIV-1 protein, the role of LMK1/CFL1-mediated actin dynamics in receptor function was studied. The effect of Nef expression on transcriptome was investigated following transfection of HEK293 cells with Nef-expressing plasmid. The array data identified Nef-induced inhibition of a number of genes that contain retinoid receptor binding sites in their promoters. The experiment was designed to study the effect of expression of HIV-1 Nef protein on gene expression levels in HEK293 cells. Cells were transfected in three different experiments (each time in duplicate) with Nef expressing plasmid and a plasmid that contained a non-expressing Nef construct (Nef/Stop) as control. The cells were harvested after 36 of transfection and processed for gene array.

2011-08-25 | E-GEOD-31665 | biostudies-arrayexpress

GTP-induced conformational changes in septins and implications for function.

Project description:Septins constitute a group of GTP-binding proteins involved in cytokinesis and other essential cellular functions. They form heterooligomeric complexes that polymerize into nonpolar filaments and are dynamic during different stages of the cell cycle. Posttranslational modifications and interacting partners are widely accepted regulators of septin filament function, but the contribution of nucleotide is undefined due to a lack of detailed structural information. Previous low-resolution structures showed that the G domain assembles into a linear polymer with 2 different interfaces involving the N and C termini and the G binding sites. Here we report the crystal structure of SEPT2 bound to GppNHp at 2.9 A resolution. GTP binding induces conformational changes in the switch regions at the G interfaces, which are transmitted to the N-terminal helix and also affect the NC interface. Biochemical studies and sequence alignment suggest that a threonine, which is conserved in certain subgroups of septins, is responsible for GTP hydrolysis. Although this threonine is not present in yeast CDC3 and CDC11, its mutation in CDC10 and CDC12 induces temperature sensitivity. Highly conserved contact residues identified in the G interface are shown to be necessary for Cdc3-10, but not Cdc11-12, heterodimer formation and cell growth in yeast. Based on our findings, we propose that GTP binding/hydrolysis and the nature of the nucleotide influence the stability of interfaces in heterooligomeric and polymeric septins and are required for proper septin filament assembly/disassembly. These data also offer a first rationale for subdividing human septins into different functional subgroups.

| S-EPMC2757862 | biostudies-literature

Reconstructing de novo silencing of an active plant retrotransposon: dynamics, mechanisms, biological implications

2013-07-02 | GSE43412 | GEO

Nucleotide-mediated conformational changes of monomeric actin and Arp3 studied by molecular dynamics simulations.

Project description:Members of the actin family of proteins exhibit different biochemical properties when ATP, ADP-P(i), ADP, or no nucleotide is bound. We used molecular dynamics simulations to study the effect of nucleotides on the behavior of actin and actin-related protein 3 (Arp3). In all of the actin simulations, the nucleotide cleft stayed closed, as in most crystal structures. ADP was much more mobile within the cleft than ATP, despite the fact that both nucleotides adopt identical conformations in actin crystal structures. The nucleotide cleft of Arp3 opened in most simulations with ATP, ADP, and no bound nucleotide. Deletion of a C-terminal region of Arp3 that extends beyond the conserved actin sequence reduced the tendency of the Arp3 cleft to open. When the Arp3 cleft opened, we observed multiple instances of partial release of the nucleotide. Cleft opening in Arp3 also allowed us to observe correlated movements of the phosphate clamp, cleft mouth, and barbed-end groove, providing a way for changes in the nucleotide state to be relayed to other parts of Arp3. The DNase binding loop of actin was highly flexible regardless of the nucleotide state. The conformation of Ser14/Thr14 in the P1 loop was sensitive to the presence of the gamma-phosphate, but other changes observed in crystal structures were not correlated with the nucleotide state on nanosecond timescales. The divalent cation occupied three positions in the nucleotide cleft, one of which was not previously observed in actin or Arp2/3 complex structures. In sum, these simulations show that subtle differences in structures of actin family proteins have profound effects on their nucleotide-driven behavior.

| S-EPMC3716381 | biostudies-literature

MC4R biased signalling and the conformational basis of biological function selections.

Project description:The MC4R, a GPCR, has long been a major target for obesity treatment. As the most well-studied melanocortin receptor subtype, the evolutionary knowledge pushes the drug development and structure-activity relationship (SAR) moving forward. The past decades have witnessed the evolution of scientists' view on GPCRs gradually from the control of a single canonical signalling pathway via a bilateral 'active-inactive' model to a multi-state alternative model where the ligands' binding affects the selection of the downstream signalling. This evolution brings the concept of biased signalling and the beginning of the next generation of peptide drug development, with the aim of turning from receptor subtype specificity to signalling pathway selectivity. The determination of the value structures of the MC4R revealed insights into the working mechanism of MC4R activation upon binding of agonists. However, new challenge has risen as we seek to unravel the mystery of MC4R signalling selection. Thus, more biased agonists and ligands with representative biological functions are needed to solve the rest of the puzzle.

| S-EPMC9344818 | biostudies-literature

Disorder transitions and conformational diversity cooperatively modulate biological function in proteins.

Project description:Structural differences between conformers sustain protein biological function. Here, we studied in a large dataset of 745 intrinsically disordered proteins, how ordered-disordered transitions modulate structural differences between conformers as derived from crystallographic data. We found that almost 50% of the proteins studied show no transitions and have low conformational diversity while the rest show transitions and a higher conformational diversity. In this last subset, 60% of the proteins become more ordered after ligand binding, while 40% more disordered. As protein conformational diversity is inherently connected with protein function our analysis suggests differences in structure-function relationships related to order-disorder transitions.

| S-EPMC4941770 | 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