• Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. (wikipedia.org)
  • Once bound to Ca2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. (wikipedia.org)
  • Calcium binding by calmodulin exhibits considerable cooperativity, making calmodulin an unusual example of a monomeric (single-chain) cooperative binding protein. (wikipedia.org)
  • Calmodulin is a small, highly conserved calcium binding protein found in all eukaryotic cells. (thermofisher.com)
  • As it binds calcium, calmodulin undergoes conformational changes which can increase its affinity for target proteins. (thermofisher.com)
  • Studies have found that calmodulin participates in the regulation of several biological processes including energy and biosynthetic metabolism, cell motility, exocytosis, cytoskeletal assembly, and intracellular modulation of both cAMP and calcium concentrations. (thermofisher.com)
  • Calcium binding induces conformational transitions in calmodulin that make it specifically active to particular target proteins. (biomedcentral.com)
  • The precise mechanisms underlying calcium binding to calmodulin are still, however, quite poorly understood. (biomedcentral.com)
  • In this study, we adopt a structural systems biology approach and develop a mathematical model to investigate various types of cooperative calcium-calmodulin interactions. (biomedcentral.com)
  • We compare the predictions of our analysis with physiological dose-response curves taken from the literature, in order to provide a quantitative comparison of the effects of different mechanisms of cooperativity on calcium-calmodulin interactions. (biomedcentral.com)
  • The results of our analysis reduce the gap between current understanding of intracellular calmodulin function at the structural level and physiological calcium-dependent calmodulin target activation experiments. (biomedcentral.com)
  • We found that Homer3, the predominant isoform in Purkinje cells, is phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) both in vitro and in vivo . (jneurosci.org)
  • In this study, we revealed that Homer3 was phosphorylated by calcium/calmodulin-dependent protein kinase II (CaMKII) in Purkinje cells, and the phosphorylation reduces the affinity for Homer target molecules, resulting in change of the solubility. (jneurosci.org)
  • Ca 2+ -binding protein calmodulin (CaM) serves as a primary effector of calcium function. (frontiersin.org)
  • The small and highly expressed Ca 2+ -binding protein calmodulin (CaM) acts as a primary effector of calcium function ( Soderling and Stull, 2001 ). (frontiersin.org)
  • They contain EF HAND MOTIFS and undergo conformational changes upon calcium-binding. (nih.gov)
  • Binding of calmodulin induces conformational rearrangements in the target protein via "mutually induced fit", leading to changes in the target protein's function. (wikipedia.org)
  • We found that calmodulin triggered only minor modifications of the protein secondary and tertiary structure but had a pronounced effect on the hydrodynamic properties of AC. (pasteur.fr)
  • We show that the C-terminal tail of Dfi1p binds to calmodulin in vitro, and mutations that affect this region affect both calmodulin binding in vitro and invasive filamentation when incorporated into the full length Dfi1p protein. (tufts.edu)
  • Once dopamine binds, the protein undergoes a conformational change, which allows both sodium and dopamine to unbind on the intracellular side of the membrane. (cloudfront.net)
  • CaM binding to the ARD triggers large conformational arrangements of DAPK1 through the disruption of the CD−ARD association, generating a constitutively active kinase. (frontiersin.org)
  • However, these nanopore sensors are mainly based on specific ligand-induced large conformational changes. (nature.com)
  • Furthermore, target binding alters the binding affinity of calmodulin toward Ca2+ ions, which allows for complex allosteric interplay between Ca2+ and target binding interactions. (wikipedia.org)
  • This influence of target binding on Ca2+ affinity is believed to allow for Ca2+ activation of proteins that are constitutively bound to calmodulin, such as small-conductance Ca2+-activated potassium (SK) channels. (wikipedia.org)
  • After the first round of purification based on the binding of ProtA to IgG-coated beads, TEV protease cleavage releases CBP-tagged bait protein along with its partners for a second round of purification on calmodulin affinity resin and leaves behind protein contaminants bound to IgG. (bvsalud.org)
  • However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. (cusabio.com)
  • Canonical" targets of calmodulin, such as myosin light-chain kinases and CaMKII, bind only to the Ca2+-bound protein, whereas some proteins, such as NaV channels and IQ-motif proteins, also bind to calmodulin in the absence of Ca2+. (wikipedia.org)
  • Together, these features allow calmodulin to recognize some 300 target proteins exhibiting a variety of CaM-binding sequence motifs. (wikipedia.org)
  • Calmodulin is an important multifunctional molecule that regulates the activities of a large number of proteins in the cell. (biomedcentral.com)
  • EF-hand Ca2+-binding proteins (CBPs), such as calmodulin (CaM) or those belonging to the S100 protein family (S100s) undergo conformational changes upon increasing intracellular Ca2+, facilitating interactions with protein targets and inducing important biological responses. (umaryland.edu)
  • 28 High-energy configurations, or conformational transition states, therefore impose discrete multi-state behavior on proteins, 21 significantly enhancing function by creating the capacity for a protein to transmit time and ligand-dependent information and/or mechanical motion necessary for signaling and other free-energy transduction processes. (aip.org)
  • With the advent, development and refining of single-molecule nanomechanical techniques that enable the conformational dynamics of individual proteins under the effect of a calibrated force to be probed, we have begun to acquire a comprehensive knowledge of the diverse physicochemical principles that regulate the elasticity of single proteins. (ibecbarcelona.eu)
  • Calmodulin is structurally quite similar to troponin C, another Ca2+-binding protein containing four EF-hand motifs. (wikipedia.org)
  • It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of calmodulin. (wikipedia.org)
  • To characterize this activation mechanism, we investigated here the biophysical properties of the isolated catalytic domain in solution with or without calmodulin. (pasteur.fr)
  • However, the mechanism underlying the influence of Ca 2+ on the conformational dynamics of the DAPK1−CaM interactions is still unclear. (frontiersin.org)
  • Here, we show that this mechanism involves calmodulin binding to the N-terminal pro-domain of Mca1, which prevents its proteolytic activation and promotes co-chaperone-like activity, thus switching from pro-cell death to anti-aging function. (bvsalud.org)
  • In order to investigate the CaM activation mechanism of nNOS, the effect of the conformational changes of nNOSrd and the binding of NADP(H) on the redox potential of the flavins, cofactors were assessed for the isolated FAD and FMN sub-domains by OTTLE potentiometry. (ndltd.org)
  • The structure of the complex between the CBD of IP3 3-K A and calmodulin allowed us to characterize the calmodulin-binding domain of IP3 3-K A. The combination of high and low-resolution data allowed us to propose a model for IP3 3-K activation upon calmodulin binding. (ucm.es)
  • We propose that conformational changes in Dfi1p in response to environmental conditions encountered during growth allow the protein to bind calmodulin and initiate a signaling cascade that activates Cek1p. (tufts.edu)
  • Conserved residues in the motor domain have been positioned within the framework provided by the recent crystal structures, thus helping to define those residues involved in actin and ATP binding, in hydrolysis and in conformational change. (embl.de)
  • The apo (1DMO [18]) (A) and Ca 2+ bound (1CLL [19]) (B) structures of the CaM protein illustrate Ca 2+ induced conformational transitions. (biomedcentral.com)
  • 39 Such conformational transitions act as molecular timers to help regulate amplitude and duration of cellular processes. (aip.org)
  • Understanding conformational transitions, however, requires characterizing the conformational transition states, an approach that is akin to understanding chemical reactions by characterizing their chemical transition states. (aip.org)
  • Crystallization and solution of free and bound to nucleotide forms of IP5 2-K allowed us the characterization of the conformational changes undergone by this enzyme during the catalytic cycle. (ucm.es)
  • For that purpose, the bait protein is translationally fused to the TAP tag, which consists of a calmodulin-binding peptide (CBP) and two immunoglobulin G (IgG)-binding domains of Staphylococcus aureus protein A (ProtA) that are separated by the tobacco etch virus (TEV) protease cleavage site. (bvsalud.org)
  • Calmodulin also exhibits great structural variability, and undergoes considerable conformational fluctuations, when bound to targets. (wikipedia.org)
  • Structural analysis further revealed that Ca 2+ removal caused the significant conformational changes at the DAPK1−CaM interface, especially the helices α1, α2, α4, α6, and α7 from the CaM and the basic loop and the phosphate-binding loop from the DAPK1. (frontiersin.org)
  • MARV assembles and buds from the host cell plasma where MARV matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane inner leaflet and undergo a dynamic and extensive self-oligomerization into the structural matrix layer. (uci.edu)
  • Although functional protein conformational change trajectories are to a degree stochastic, they nonetheless pass through a well-defined transition state whose detailed structural properties can rapidly be identified using PATH. (aip.org)
  • The structural reaction profile of Geobacillus stearothermophilus tryptophanyl-tRNA synthetase (TrpRS) involves three conformationally distinct states 6 that impose rate-limiting conformational changes. (aip.org)
  • Though such ions distort calmodulin's structure and are generally not physiologically relevant due to their scarcity in vitro, they have nonetheless seen wide scientific use as reporters of calmodulin structure and function. (wikipedia.org)
  • In vitro selection of RNAs that undergo autolytic cleavage with Pb2+. (colorado.edu)
  • Most of the mechanisms of motion rely on the conformational change of some molecule (usually a protein), and so unsurprisingly there are a huge range of different mechanisms available, often developed independently of each other and therefore cardinally different from one another even where they look the same and do exactly the same thing. (derangedphysiology.com)
  • From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (bvsalud.org)
  • However, troponin C contains an additional alpha-helix at its N-terminus, and is constitutively bound to its target, troponin I. It therefore does not exhibit the same diversity of target recognition as does calmodulin. (wikipedia.org)
  • "It was expected answers would describe in detail the role of troponin, tropomyosin and calmodulin in mediating muscle contraction" , the examiners rejoined. (derangedphysiology.com)
  • However, as the structure of the catalytic domain in the absence of calmodulin is still lacking, the molecular basis of AC activation by calmodulin remains largely unknown. (pasteur.fr)
  • Integrins are obligatory type I αβ heterodimers and molecular MLN8237 (Alisertib) devices that undergo huge conformational adjustments within their extracellular domains brought about by signaling substances inside cells. (tam-receptor.com)
  • Two key points in the metabolism of IPs were analysed during this work: the regulation by Ca2+/ calmodulin of IP3 3-K (the starting point for the synthesis of IPs) and the structure of the IP5 2-K (the enzyme responsible for the synthesis of IP6). (ucm.es)
  • Results showed that the specificity of NADPH in inducing nNOS rd conformational change relies upon the interaction of both the tightly-bound ADP substituents and the labile nicotinamide substituents and that the tightly bound ADP substituents is essential to position the nicotinamide moieties for full electron transfer repression. (ndltd.org)
  • Moreover, the predominantly hydrophobic nature of binding between calmodulin and most of its targets allows for recognition of a broad range of target protein sequences. (wikipedia.org)
  • The flexible central domain of calmodulin allows the protein to wrap around its target, although alternate modes of binding are known. (wikipedia.org)
  • Although calmodulin principally operates as a Ca2+ binding protein, it also coordinates other metal ions. (wikipedia.org)
  • Dfi1p Binding to Calmodulin Promotes Filamentation and Cek1p Activation in Candida albicans. (tufts.edu)
  • The C-terminal tail of Dfi1p has a calmodulin binding motif, suggesting that Dfi1p binding to calmodulin may affect Cek1p activation and invasive filamentation. (tufts.edu)
  • The goal of this work was to determine the importance of the calmodulin binding motif of Dfi1p in filamentation and signaling. (tufts.edu)
  • In addition to the flexibility of the central linker domain, the N- and C-domains undergo open-closed conformational cycling in the Ca2+-bound state. (wikipedia.org)
  • CaM presents two conformational architectures, including the collapsed and the extended forms, because of the flexibility of CaM's linker. (frontiersin.org)
  • For most if not absolutely all integrins such conformational adjustments ("activation") must actuate their adhesive function. (tam-receptor.com)
  • Abstract: Candida albicans, a dimorphic fungus and human opportunistic pathogen, undergoes hyphal development in response to many different environmental cues, including growth in contact with a semi-solid matrix. (tufts.edu)
  • Computational treatments of protein conformational changes tend to focus on the trajectories themselves, despite the fact that it is the transition state structures that contain information about the barriers that impose multi-state behavior. (aip.org)
  • Structures of conformational transition states should therefore reveal valuable information about the energy barriers that separate one equilibrium structure from another. (aip.org)
  • When psychosine was supplied to proliferating cells, cells underwent special type of mitosis, endomitosis, which sustains cellular content duplication without segregation, resulted in the giant and multiploid cell formation. (sphingolipidclub.com)
  • The structure of AC in complex with the C-terminal part of calmodulin has recently been determined. (pasteur.fr)
  • This process is essential in ensuring an adequate concentration of required components is maintained at sites undergoing rapid or modulation, or where a specific subcellular process is being carried out. (mechanobio.info)
  • Slower, protein conformational changes can be rate-limiting even if the catalyzed chemical reaction is rapid. (aip.org)