Proteins with calmodulin-like domains: structures and functional roles

Villalobo, Antonio; González‐Muñoz, María José; Berchtold, Martin W.

doi:10.1007/s00018-019-03062-z

Cited by 38 publications

(25 citation statements)

References 285 publications

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“…The EF-hand domain belongs to the superfamily of calmodulin (CaM), occurring widely in proteins from different organisms, such as bacteria, plants, and animals [ 49 ]. Many environmental factors can cause the flow of Ca 2+ between the cytoplasm and subcellular organelles, to act as the secondary messenger [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Biochemical Characterization and Crystal Structure of a Novel NAD+-Dependent Isocitrate Dehydrogenase from Phaeodactylum tricornutum

Huang¹,

Zhou²,

Wen³

et al. 2020

IJMS

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The marine diatom Phaeodactylum tricornutum originated from a series of secondary symbiotic events and has been used as a model organism for studying diatom biology. A novel type II homodimeric isocitrate dehydrogenase from P. tricornutum (PtIDH1) was expressed, purified, and identified in detail through enzymatic characterization. Kinetic analysis showed that PtIDH1 is NAD+-dependent and has no detectable activity with NADP+. The catalytic efficiency of PtIDH1 for NAD+ is 0.16 μM−1·s−1 and 0.09 μM−1·s−1 in the presence of Mn2+ and Mg2+, respectively. Unlike other bacterial homodimeric NAD-IDHs, PtIDH1 activity was allosterically regulated by the isocitrate. Furthermore, the dimeric structure of PtIDH1 was determined at 2.8 Å resolution, and each subunit was resolved into four domains, similar to the eukaryotic homodimeric NADP-IDH in the type II subfamily. Interestingly, a unique and novel C-terminal EF-hand domain was first defined in PtIDH1. Deletion of this domain disrupted the intact dimeric structure and activity. Mutation of the four Ca2+-binding sites in the EF-hand significantly reduced the calcium tolerance of PtIDH1. Thus, we suggest that the EF-hand domain could be involved in the dimerization and Ca2+-coordination of PtIDH1. The current report, on the first structure of type II eukaryotic NAD-IDH, provides new information for further investigation of the evolution of the IDH family.

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Section: Discussionmentioning

confidence: 99%

Biochemical Characterization and Crystal Structure of a Novel NAD+-Dependent Isocitrate Dehydrogenase from Phaeodactylum tricornutum

Huang¹,

Zhou²,

Wen³

et al. 2020

IJMS

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“…For a focused review on the roles of CaM in a cardiomyocyte, see Sorensen et al 2013 [3]. Despite being one of the most widely investigated proteins, there are still considerable knowledge gaps that limit our understanding of Ca 2+ -induced modification of CaM, and the proteins whose activity is regulated or modified by it [4].…”

Section: Introductionmentioning

confidence: 99%

Calmodulin Mutations Associated with Heart Arrhythmia: A Status Report

Chazin

Johnson

2020

IJMS

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Calmodulin (CaM) is a ubiquitous intracellular Ca2+ sensing protein that modifies gating of numerous ion channels. CaM has an extraordinarily high level of evolutionary conservation, which led to the fundamental assumption that mutation would be lethal. However, in 2012, complete exome sequencing of infants suffering from recurrent cardiac arrest revealed de novo mutations in the three human CALM genes. The correlation between mutations and pathophysiology suggests defects in CaM-dependent ion channel functions. Here, we review the current state of the field for all reported CaM mutations associated with cardiac arrhythmias, including knowledge of their biochemical and structural characteristics, and progress towards understanding how these mutations affect cardiac ion channel function.

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“…They are involved in many important cellular pathways due to their interactions with target messengers/receptors. The interactions of CaM or S100A1 with target-binding epitopes have been deeply analysed in the past [ 15 , 16 , 17 ]. Initially, these interactions are mediated through nonspecific long-range electrostatic interactions of negatively charged residues of CaM or S100A1 and positively charged residues from the binding epitopes of target receptors.…”

Section: Introductionmentioning

confidence: 99%

“…Specific contacts are then formed between the so-called hydrophobic anchors from binding epitopes and dedicated hydrophobic cavities of CaM or S100A1. The specific positions of hydrophobic amino acids (either 1-5-10 and/or 1-8-14 [ 13 , 17 , 18 , 19 ]) are used for the bioinformatic identification of potential CaM-binding sites [ 17 ]. Indeed, several such binding sites have been proposed in the proximal C-terminal region of TRPM4 [ 12 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Mapping of CaM, S100A1 and PIP2-Binding Epitopes in the Intracellular N- and C-Termini of TRPM4

Boušová

Barvı́k

Heřman

et al. 2020

IJMS

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Molecular determinants of the binding of various endogenous modulators to transient receptor potential (TRP) channels are crucial for the understanding of necessary cellular pathways, as well as new paths for rational drug designs. The aim of this study was to characterise interactions between the TRP cation channel subfamily melastatin member 4 (TRPM4) and endogenous intracellular modulators—calcium-binding proteins (calmodulin (CaM) and S100A1) and phosphatidylinositol 4, 5-bisphosphate (PIP2). We have found binding epitopes at the N- and C-termini of TRPM4 shared by CaM, S100A1 and PIP2. The binding affinities of short peptides representing the binding epitopes of N- and C-termini were measured by means of fluorescence anisotropy (FA). The importance of representative basic amino acids and their combinations from both peptides for the binding of endogenous TRPM4 modulators was proved using point alanine-scanning mutagenesis. In silico protein–protein docking of both peptides to CaM and S100A1 and extensive molecular dynamics (MD) simulations enabled the description of key stabilising interactions at the atomic level. Recently solved cryo-Electron Microscopy (EM) structures made it possible to put our findings into the context of the entire TRPM4 channel and to deduce how the binding of these endogenous modulators could allosterically affect the gating of TRPM4. Moreover, both identified binding epitopes seem to be ideally positioned to mediate the involvement of TRPM4 in higher-order hetero-multimeric complexes with important physiological functions.

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Proteins with calmodulin-like domains: structures and functional roles

Cited by 38 publications

References 285 publications

Biochemical Characterization and Crystal Structure of a Novel NAD+-Dependent Isocitrate Dehydrogenase from Phaeodactylum tricornutum

Biochemical Characterization and Crystal Structure of a Novel NAD+-Dependent Isocitrate Dehydrogenase from Phaeodactylum tricornutum

Calmodulin Mutations Associated with Heart Arrhythmia: A Status Report

Mapping of CaM, S100A1 and PIP2-Binding Epitopes in the Intracellular N- and C-Termini of TRPM4

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