Calcium-Binding Proteins: Intracellular Sensors from the Calmodulin Superfamily

Haeseleer, Françoise; Imanishi, Yoshikazu; Sokal, Izabela; Filipek, Sławomir; Palczewski, Krzysztof

doi:10.1006/bbrc.2001.6228

Cited by 148 publications

(116 citation statements)

References 74 publications

(63 reference statements)

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“…The recombinant CaBP1 protein was cloned into a pET3b vector and expressed in Escherichia coli BL21(DE3) cells as described previously. 23 Uniformly 13 C/ 15 N-labeled protein expression was induced by the addition of 0.5 mM IPTG at 37 C in M9 minimal medium containing 15 NH 4 Cl and U-13 C glucose. Cells obtained from M9 cultures were disrupted by sonication.…”

Section: Sample Preparationmentioning

confidence: 99%

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition

Park

Ames

2011

Protein Science

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Calcium-binding protein 1 (CaBP1), a neuron-specific member of the calmodulin (CaM) superfamily, regulates the Ca 21 -dependent activity of inositol 1,4,5-triphosphate receptors (InsP3Rs) and various voltage-gated Ca 21 channels. Here, we present the NMR structure of fulllength CaBP1 with Ca 21 bound at the first, third, and fourth EF-hands. A total of 1250 nuclear Overhauser effect distance measurements and 70 residual dipolar coupling restraints define the overall main chain structure with a root-mean-squared deviation of 0.54 Å (N-domain) and 0.48 Å (C-domain). The first 18 residues from the N-terminus in CaBP1 (located upstream of the first EFhand) are structurally disordered and solvent exposed. The Ca 21 -saturated CaBP1 structure contains two independent domains separated by a flexible central linker similar to that in calmodulin and troponin C. The N-domain structure of CaBP1 contains two EF-hands (EF1 and EF2), both in a closed conformation [interhelical angles 5 129°(EF1) and 142°(EF2)]. The C-domain contains EF3 and EF4 in the familiar Ca 21 -bound open conformation [interhelical angles 5 105°( EF3) and 91°(EF4)]. Surprisingly, the N-domain adopts the same closed conformation in the presence or absence of Ca 21 bound at EF1. The Ca 21 -bound closed conformation of EF1 is reminiscent of Ca 21 -bound EF-hands in a closed conformation found in cardiac troponin C and calpain. We propose that the Ca 21 -bound closed conformation of EF1 in CaBP1 might undergo an induced-fit opening only in the presence of a specific target protein, and thus may help explain the highly specialized target binding by CaBP1.

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Section: Sample Preparationmentioning

confidence: 99%

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition

Park

Ames

2011

Protein Science

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“…As is characteristic of other members of the CaM-like Ca 2ϩ -binding proteins, Scarf is an acidic protein (pI ϭ 4.59) with no cysteine or tryptophan residues. A particular difference with calcium-binding proteins (13,14) is that Scarf does not present putative sites for myristoylation. Comparison of the four EF-hand motifs of Scarf and other CaM-like proteins showed high homology in the EF-2, -3, and -4 motifs, with EF-1 being the most divergent (Fig.…”

Section: Scarf Cloning and Genomic And Protein Characterization-amentioning

confidence: 99%

“…The functions of many proteins involved in cell signaling by phosphorylation/dephosphorylation or in the modulation of intracellular levels of second messengers are reportedly CaM-dependent (12). Recently, several Ca 2ϩ -binding proteins with structural homology to CaM have been reported: calcium-binding proteins (CaBPs) (13,14), hClp (15), and the human skin-specific hClsp (16,17).…”

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confidence: 99%

The Novel Murine Ca2+-binding Protein, Scarf, Is Differentially Expressed during Epidermal Differentiation

Hwang

Morasso

2003

Journal of Biological Chemistry

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Keratinocytes follow a complex program of differentiation from the basal layer to the spinous and granular layers of the epidermis, which ultimately leads to the formation of a waterimpermeable barrier. The final phase in epidermal differentiation is characterized by granular cell death, destruction of organelles, covalent cross-linking of cornified envelope precursors by Ca 2ϩ -dependent transglutaminases (TGases), 1 and attachment of lipid molecules to the cross-linked envelopes (1). This program is accomplished through specific transcriptional induction and repression of structural and enzymatic differentiation-specific markers (2). The differentiation process can be recapitulated partially in mouse keratinocytes cultivated in vitro by increasing the Ca 2ϩ concentration in the culture medium (3) and is associated with the activation of protein kinase C (PKC) (4). This produces a situation that mimics the endogenous Ca 2ϩ gradient present in the skin, with low extracellular levels surrounding the basal cells and increasing levels toward the upper granular layers (5). The ability to induce differentiation in primary cultured keratinocytes, along with the presence of a Ca 2ϩ gradient, underscores the importance of this ion and the Ca 2ϩ -dependent signaling pathways in the epidermis.A crucial role for the transduction of the Ca 2ϩ signal is accomplished by members of the Ca 2ϩ -binding proteins, which are characterized by the presence of a common helix-loop-helix structural motif in their Ca 2ϩ -binding domain, termed EFhand (6). These proteins function by undergoing conformational changes upon binding of Ca 2ϩ , allowing the association and regulation of activity of a range of specific target proteins. EF-hand-containing proteins have been described in epidermis; these include the large proteins profilaggrin and repetin (7,8), which present EF-hand motifs in the NH 2 -terminal region followed by multiple tandem repeats and members of the dimeric EF-hand S100 multigenic family (9 -11). The best studied of the Ca 2ϩ -signaling proteins is CaM, a small, highly conserved, and ubiquitous protein that is crucial to many Ca 2ϩ -dependent processes in eukaryotes (6, 12). The functions of many proteins involved in cell signaling by phosphorylation/dephosphorylation or in the modulation of intracellular levels of second messengers are reportedly CaM-dependent (12). Recently, several Ca 2ϩ -binding proteins with structural homology to CaM have been reported: calcium-binding proteins (CaBPs) (13, 14), hClp (15), and the human skin-specific hClsp (16,17).We present the cloning, genomic structure, expression, and functional assay for a novel mouse Ca 2ϩ -binding protein that we have termed Scarf. The Scarf open reading frame (ORF) codes for a small protein with four EF-hand Ca 2ϩ -binding domains. The Scarf gene and protein are differentially expressed in vivo in the spinous and granular layers of the epidermis. We also present the identification of a second highly homologous gene, Scarf2, which localizes 15 kb downstream fr...

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“…Many cytoplasmic Ca 2ϩ -binding proteins mediate the intracellular actions of Ca 2ϩ (Südhof and Rizo, 1996;Haeseleer et al, 2002;Burgoyne et al, 2004;Mikhaylova et al, 2006). Among these Ca 2ϩ -binding proteins, calmodulin (CaM) is likely the most important but also the most enigmatic (Chin and Means, 2000).…”

Section: Introductionmentioning

confidence: 99%

Calmodulin Controls Synaptic Strength via Presynaptic Activation of Calmodulin Kinase II

Pang¹,

Cao²,

Xu³

et al. 2010

J. Neurosci.

101

112

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Calmodulin regulates multifarious cellular processes via a panoply of target interactions. However, the central role, multiple isoforms, and complex target interactions of calmodulin make it difficult to examine its precise functions. Here, we analyzed calmodulin function in neurons using lentivirally delivered short-hairpin RNAs that suppressed expression of all calmodulin isoforms by ϳ70%. Calmodulin knockdown did not significantly alter neuronal survival or synapse formation but depressed spontaneous neuronal network activity. Strikingly, calmodulin knockdown decreased the presynaptic release probability almost twofold, without altering the presynaptic readily-releasable vesicle pool or postsynaptic neurotransmitter reception. In calmodulin knockdown neurons, presynaptic release was restored to wild-type levels by expression of constitutively active calmodulin-dependent kinase-II␣ (CaMKII␣); in contrast, in control neurons, expression of constitutively active CaMKII␣ had no effect on presynaptic release. Viewed together, these data suggest that calmodulin performs a major function in boosting synaptic strength via direct activation of presynaptic calmodulin-dependent kinase II.

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Calcium-Binding Proteins: Intracellular Sensors from the Calmodulin Superfamily

Cited by 148 publications

References 74 publications

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition

The Novel Murine Ca2+-binding Protein, Scarf, Is Differentially Expressed during Epidermal Differentiation

Calmodulin Controls Synaptic Strength via Presynaptic Activation of Calmodulin Kinase II

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Calcium-Binding Proteins: Intracellular Sensors from the Calmodulin Superfamily

Cited by 148 publications

References 74 publications

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca2+‐bound closed state: Implications for target recognition

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca2+‐bound closed state: Implications for target recognition

The Novel Murine Ca2+-binding Protein, Scarf, Is Differentially Expressed during Epidermal Differentiation

Calmodulin Controls Synaptic Strength via Presynaptic Activation of Calmodulin Kinase II

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Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca²⁺‐bound closed state: Implications for target recognition