The C‐terminal calcium‐sensitive disordered motifs regulate isoform‐specific polymerization characteristics of calsequestrin

Bal, Naresh C.; Jena, Nivedita; Chakravarty, Harapriya; Kumar, Amit; Chi, Mei; Balaraju, Tuniki; Rawale, Sharad; Rawale, Jayashree S.; Sharon, Ashoke; Periasamy, Muthu

doi:10.1002/bip.22534

Cited by 14 publications

(14 citation statements)

References 51 publications

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“…Calsequestrin, is a sarcoplamic reticulum protein of skeletal and cardiac muscle [ 38 ]. It binds 40–50 calcium ions per molecule.…”

Section: Calcium-binding Idpsmentioning

confidence: 99%

Calcium-Binding Proteins with Disordered Structure and Their Role in Secretion, Storage, and Cellular Signaling

Grzybowska

2018

Biomolecules

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Calcium is one of the most important second messengers and its intracellular signaling regulates many aspects of cell physiology. Calcium ions, like phosphate ions, are highly charged and thus are able to alter protein conformation upon binding; thereby they constitute key factors in signal transduction. One of the most common calcium-binding structural motifs is the EF-hand, a well-defined helix-loop-helix structural domain, present in many calcium-binding proteins (CBPs). Nonetheless, some CBPs contain non-canonical, disordered motifs, which usually bind calcium with high capacity and low affinity, and which represent a subset of proteins with specific functions, but these functions rarely involve signaling. When compared with phosphorylation-mediated signal transduction, the role of intrinsic disorder in calcium signaling is significantly less prominent and not direct. The list of known examples of intrinsically disordered CBPs is relatively short and the disorder in these examples seems to be linked to secretion and storage. Calcium-sensitive phosphatase calcineurin is an exception, but it represents an example of transient disorder, which is, nevertheless, vital to the functioning of this protein. The underlying reason for the different role of disordered proteins in the two main cellular signaling systems appears to be linked to the gradient of calcium concentration, present in all living cells.

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“…Calsequestrin, is a sarcoplamic reticulum protein of skeletal and cardiac muscle [ 38 ]. It binds 40–50 calcium ions per molecule.…”

Section: Calcium-binding Idpsmentioning

confidence: 99%

Calcium-Binding Proteins with Disordered Structure and Their Role in Secretion, Storage, and Cellular Signaling

Grzybowska

2018

Biomolecules

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“…CSQ1 and CSQ2 undergo Ca 2+ -induced compaction or a shift from the proteins soluble to insoluble form [ 41 ]. CSQ1 aggregation is measured as turbidity (absorbance at 350 nm), which is proportional to the levels of insoluble CSQ1 [ 40 , 41 ]. The turbidity of WT CSQ1 increases sigmoidily across the [Ca 2+ ] range tested, reaching a constant concentration of insoluble protein at between 1 and 1.5 mM Ca 2+ (Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Solution turbidity [ 40 , 41 ] was monitored spectrophotometrically in a 1-cm path length quartz cuvette. Three micromolar protein was suspended in a buffer containing 20 mM Tris and 100 mM KCl pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

C-terminal residues of skeletal muscle calsequestrin are essential for calcium binding and for skeletal ryanodine receptor inhibition

Beard

Dulhunty

2015

Skeletal Muscle

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BackgroundSkeletal muscle function depends on calcium signaling proteins in the sarcoplasmic reticulum (SR), including the calcium-binding protein calsequestrin (CSQ), the ryanodine receptor (RyR) calcium release channel, and skeletal triadin 95 kDa (trisk95) and junctin, proteins that bind to calsequestrin type 1 (CSQ1) and ryanodine receptor type 1 (RyR1). CSQ1 inhibits RyR1 and communicates store calcium load to RyR1 channels via trisk95 and/or junctin.MethodsIn this manuscript, we test predictions that CSQ1’s acidic C-terminus contains binding sites for trisk95 and junctin, the major calcium binding domain, and that it determines CSQ1’s ability to regulate RyR1 activity.ResultsProgressive alanine substitution of C-terminal acidic residues of CSQ1 caused a parallel reduction in the calcium binding capacity but did not significantly alter CSQ1’s association with trisk95/junctin or influence its inhibition of RyR1 activity. Deletion of the final seven residues in the C-terminus significantly hampered calcium binding, significantly reduced CSQ’s association with trisk95/junctin and decreased its inhibition of RyR1. Deletion of the full C-terminus further reduced calcium binding to CSQ1 altered its association with trisk95 and junctin and abolished its inhibition of RyR1.ConclusionsThe correlation between the number of residues mutated/deleted and binding of calcium, trisk95, and junctin suggests that binding of each depends on diffuse ionic interactions with several C-terminal residues and that these interactions may be required for CSQ1 to maintain normal muscle function.

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“…Moreover, X-ray resolution of the human and rabbit Casq tetramer linked to Ca 2? (Kumar et al 2013) and COOH-terminal biophysical studies (Bal et al 2015) show that Casq monomer folding is not influenced by the COOH-terminal. Kumar et al (2013) also found that eight high affinity Ca 2?…”

Section: Zebrafish Calsquestrins Change Conformation In the Presence mentioning

confidence: 97%

Calsequestrins in skeletal and cardiac muscle from adult Danio rerio

Furlan

Mosole

Murgia

et al. 2015

J Muscle Res Cell Motil

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Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located.

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The C‐terminal calcium‐sensitive disordered motifs regulate isoform‐specific polymerization characteristics of calsequestrin

Cited by 14 publications

References 51 publications

Calcium-Binding Proteins with Disordered Structure and Their Role in Secretion, Storage, and Cellular Signaling

Calcium-Binding Proteins with Disordered Structure and Their Role in Secretion, Storage, and Cellular Signaling

C-terminal residues of skeletal muscle calsequestrin are essential for calcium binding and for skeletal ryanodine receptor inhibition

Calsequestrins in skeletal and cardiac muscle from adult Danio rerio

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