Modulation of Calmodulin Lobes by Different Targets: An Allosteric Model with Hemiconcerted Conformational Transitions

  title={Modulation of Calmodulin Lobes by Different Targets: An Allosteric Model with Hemiconcerted Conformational Transitions},
  author={Massimo Lai and Denis Brun and Stuart J. Edelstein and Nicolas Le Nov{\`e}re},
  journal={PLoS Computational Biology},
Calmodulin is a calcium-binding protein ubiquitous in eukaryotic cells, involved in numerous calcium-regulated biological phenomena, such as synaptic plasticity, muscle contraction, cell cycle, and circadian rhythms. It exibits a characteristic dumbell shape, with two globular domains (N- and C-terminal lobe) joined by a linker region. Each lobe can take alternative conformations, affected by the binding of calcium and target proteins. Calmodulin displays considerable functional flexibility due… 

The mechanism of complex formation between calmodulin and voltage gated calcium channels revealed by molecular dynamics

A unique intermediate conformation of Ca2+/CaM while transitioning from extended to compact form is reported, and how IQ motif recognise its binding site on the CaM and how CaM transforms from extendedto compact form upon binding to IQ motif is reported.

Neurogranin Stimulates Ca2+/calmodulin-dependent Kinase II by Inhibiting Calcineurin at Specific Calcium Spike Frequencies

Calmodulin sits at the centre of molecular mechanisms underlying learning and memory. Its complex, and sometimes opposite influences, via the binding to various proteins, are yet to be fully

Neurogranin stimulates Ca2+/calmodulin-dependent kinase II by suppressing calcineurin activity at specific calcium spike frequencies

Calmodulin sits at the center of molecular mechanisms underlying learning and memory. Its complex and sometimes opposite influences, mediated via the binding to various proteins, are yet to be fully

Biophysical attributes that affect CaMKII activation deduced with a novel spatial stochastic simulation approach

The findings suggest that particular intracellular environmental factors such as crowding and calmodulin availability can play an important role in decoding Ca2+ signals and can give rise to distinct CaMKII activation patterns in dendritic spines,Ca2+ channel nanodomains and cytoplasm.

Calmodulin as Ca2+-Dependent Interactor of FTO Dioxygenase

Calmodulin is indicated as a new FTO interactor and support engagement of the FTO protein in calcium signaling pathways and the modeling of FTO–CaM interaction showed its stable structure when the half of the CaM molecule saturated with Ca2+ interacts with the Fto C-domain, whereas the other part is disconnected.

Functional basis for calmodulation of the TRPV5 calcium channel

It is demonstrated for the first time that functional (full-length) TRPV5 interacts with CaM in the absence of Ca2+, and this interaction is intensified at increasing Ca2+ concentrations sensed by the CaM C-lobe that achieves channel pore blocking.

Coarse-grained molecular simulations of allosteric cooperativity.

The structural origins of binding affinity and allosteric cooperativity of binding two Ca(2+) ions to each domain of Calmodulin (CaM) are investigated through simulations of a simple coarse-grained model.



An allosteric model of calmodulin explains differential activation of PP2B and CaMKII

An allosteric model for calmodulin activation is proposed, in which binding to calcium facilitates the transition between a low-affinity [tense (T)] and a high-Affinity [relaxed (R] state, and the four calcium-binding sites are assumed to be nonidentical.

Blocking the Ca-induced Conformational Transitions in Calmodulin with Disulfide Bonds (*)

Results indicate that the Ca-induced opening of the interfaces between helical segments in both domains of CaM is critical for its regulatory properties consistent with the Herzberg-Moult-James model.

Recognition of β–calcineurin by the domains of calmodulin: Thermodynamic and structural evidence for distinct roles

Structural and thermodynamic properties would permit the domains of CaM to have distinct physiological roles in regulating activation of βCaN, and to preserve intrinsic domain differences, and the preference of calcium for sites III and IV.

A Novel Trans Conformation of Ligand-Free Calmodulin

This report reports the crystal structure of a novel trans conformation of ligand-free CaM where the relative disposition of two lobes of CaM is different, a conformation to-date not reported.

Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: Two ways to promote multifunctionality

  • M. IkuraJ. Ames
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
The essence of molecular recognition activities and the mechanisms by which calmodulin superfamily proteins control a wide variety of Ca2+ signaling processes are examined.

Structure of a trapped intermediate of calmodulin: calcium regulation of EF-hand proteins from a new perspective.

  • Z. Grabarek
  • Chemistry, Biology
    Journal of molecular biology
  • 2005

Molecular Tuning of an EF-Hand-like Calcium Binding Loop

A structurally homologous Ca2+ binding loop is used as a model for the EF-loop in studies examining the contribution of the third loop position to intramolecular tuning, supporting a model in which large-ion size selectivity is controlled by complex interactions between multiple side chains rather than by the dimensions of a single coordinating side chain.

A New Role for IQ Motif Proteins in Regulating Calmodulin Function*

It is shown that PEP-19 accelerates by 40 to 50-fold both the slow association and dissociation of Ca2+ from the C-domain of free CaM, and the sites of interaction between CaM and P EP-19 are identified using NMR.