Molecular Dynamics Study of the Changes in Conformation of Calmodulin with Calcium Binding and/or Target Recognition

Kawasaki, Hiroshi; Soma, Natsumi; Kretsinger, Robert H.

doi:10.1038/s41598-019-47063-1

Cited by 21 publications

(13 citation statements)

References 31 publications

(38 reference statements)

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“…Multivalent ions can cause changes in the sizes of the polyelectrolyte chains and alter their local conformations. It has been shown that Ca 2+ ions can induce specific secondary structures in different peptides not only by screening electrostatics but also by forming ion bridges between anionic monomers [39][40][41]. We have performed atomistic MD simulations to investigate the effects of CaCl2 salt on conformations of PASA and PGA.…”

Section: Introductionmentioning

confidence: 99%

Influence of Calcium Binding on Conformations and Motions of Anionic Polyamino Acids. Effect of Side Chain Length

et al. 2020

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Investigation of the effect of CaCl2 salt on conformations of two anionic poly(amino acids) with different side chain lengths, poly-(α-l glutamic acid) (PGA) and poly-(α-l aspartic acid) (PASA), was performed by atomistic molecular dynamics (MD) simulations. The simulations were performed using both unbiased MD and the Hamiltonian replica exchange (HRE) method. The results show that at low CaCl2 concentration adsorption of Ca2+ ions lead to a significant chain size reduction for both PGA and PASA. With the increase in concentration, the chains sizes partially recover due to electrostatic repulsion between the adsorbed Ca2+ ions. Here, the side chain length becomes important. Due to the longer side chain and its ability to distance the charged groups with adsorbed ions from both each other and the backbone, PGA remains longer in the collapsed state as the CaCl2 concentration is increased. The analysis of the distribution of the mineral ions suggests that both poly(amino acids) should induce the formation of mineral with the same structure of the crystal cell.

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Section: Introductionmentioning

confidence: 99%

Influence of Calcium Binding on Conformations and Motions of Anionic Polyamino Acids. Effect of Side Chain Length

et al. 2020

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“…Each of these globular clusters can bind up to two free Ca 2+ ions via a pair of helix-loop-helix motives (EF-hands) in a cooperative manner (K d = 5 · 10 −7 M to 5 · 10 −6 M) [ 16 , 17 , 18 ]. Because of subtle structural differences between these lobes resulting from evolutionary processes [ 19 ], EF hands in the C-lobe exhibit a three- to five times higher affinity for Ca 2+ . However, they possess slower rate of ion binding than the regions of EF hands located in the N-lobe, establishing the broad range of CaM sensitivity to the changes in calcium concentrations in the intracellular space [ 20 ].…”

Section: Calmodulin—ubiquitous Ca 2+ Sensor In mentioning

confidence: 99%

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

Boczek

Sobolczyk

Mackiewicz

et al. 2021

IJMS

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Calcium in mammalian neurons is essential for developmental processes, neurotransmitter release, apoptosis, and signal transduction. Incorrectly processed Ca2+ signal is well-known to trigger a cascade of events leading to altered response to variety of stimuli and persistent accumulation of pathological changes at the molecular level. To counterbalance potentially detrimental consequences of Ca2+, neurons are equipped with sophisticated mechanisms that function to keep its concentration in a tightly regulated range. Calcium pumps belonging to the P-type family of ATPases: plasma membrane Ca2+-ATPase (PMCA), sarco/endoplasmic Ca2+-ATPase (SERCA) and secretory pathway Ca2+-ATPase (SPCA) are considered efficient line of defense against abnormal Ca2+ rises. However, their role is not limited only to Ca2+ transport, as they present tissue-specific functionality and unique sensitive to the regulation by the main calcium signal decoding protein—calmodulin (CaM). Based on the available literature, in this review we analyze the contribution of these three types of Ca2+-ATPases to neuropathology, with a special emphasis on mental diseases.

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“…In order to overcome the limitations imposed by analyzing static crystal structures, we have employed molecular dynamics (MD) simulations to probe the RyR2–CaM binding interface at the level of individual amino acid residues. Aside from the RyR2–CaM system, several previous studies have used MD simulations to explore the dynamics and binding interactions of CaM and other CaM-like proteins with various peptide targets. − As an important test case, we have modeled our computational study after an experiment carried out by Nakamura et al…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis of Binding Interactions between the Ryanodine Receptor Type 2 and Calmodulin

et al. 2021

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Mutations in the cardiac ryanodine receptor type 2 (RyR2) have been linked to a variety of cardiac arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). RyR2 is regulated by calmodulin (CaM), and mutations that disrupt their interaction can cause aberrant calcium release, leading to an arrhythmia. It was recently shown that increasing the RyR2–CaM binding affinity could rescue a defective CPVT-related RyR2 channel to near wild-type behavior. However, the interactions that determine the binding affinity at the RyR2–CaM binding interface are not well understood. In this study, we identify the key domains and interactions, including several new interactions, involved in the binding of CaM to RyR2. Also, our comparison between the wild-type and V3599K mutant suggests how the RyR2–CaM binding affinity can be increased via a change in the central and N-terminal lobe binding contacts for CaM. This computational approach provides new insights into the effect of a mutation at the RyR2–CaM binding interface, and it may find utility in drug design for the future treatment of cardiac arrhythmias.

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Molecular Dynamics Study of the Changes in Conformation of Calmodulin with Calcium Binding and/or Target Recognition

Cited by 21 publications

References 31 publications

Influence of Calcium Binding on Conformations and Motions of Anionic Polyamino Acids. Effect of Side Chain Length

Influence of Calcium Binding on Conformations and Motions of Anionic Polyamino Acids. Effect of Side Chain Length

Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases

Computational Analysis of Binding Interactions between the Ryanodine Receptor Type 2 and Calmodulin

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