Phosphorylation of human calsequestrin: implications for calcium regulation

Emiliano J Sanchez; Gerhard R Munske; Angela Criswell; Hendrik Milting; A Keith Dunker; Chulhee Kang

doi:10.1007/s11010-011-0787-4

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Phosphorylation of human calsequestrin: implications for calcium regulation

Journal article

Peer reviewed

Phosphorylation of human calsequestrin: implications for calcium regulation

Emiliano J Sanchez, Gerhard R Munske, Angela Criswell, Hendrik Milting, A Keith Dunker and Chulhee Kang

Molecular and cellular biochemistry, Vol.353(1-2), pp.195-204

07/2011

DOI: https://doi.org/10.1007/s11010-011-0787-4

Handle:

https://hdl.handle.net/2376/110873

PMID: 21416293

Abstract

Phosphorylation

Calcium - metabolism

Humans

Molecular Sequence Data

Calsequestrin - genetics

X-Ray Diffraction

Mass Spectrometry

Sarcoplasmic Reticulum - metabolism

Calsequestrin - metabolism

Circular Dichroism

Protein Structure, Tertiary

Amino Acid Sequence

Protein Structure, Secondary

Models, Molecular

Scattering, Small Angle

Serine - genetics

Binding Sites - genetics

Phosphoserine - metabolism

Serine - chemistry

Calsequestrin - chemistry

Serine - metabolism

Sequence Homology, Amino Acid

Protein Binding

Phosphoserine - chemistry

Amino Acid Substitution

Both cardiac and skeletal calsequestrin (CASQ2 and CASQ1) serve as a major Ca(2+) storage/buffer protein in the sarcoplasmic reticulum (SR) by sequestering and releasing large numbers of Ca(2+) ions during each muscular contraction and relaxation cycle. CASQ isolated from various species often exists in a phosphorylated form, but phosphorylation's role is not yet understood. Here, the authors identified two phosphorylation sites, Ser(385) and Ser(393), for the first time, in human CASQ2 (hCASQ2) by mass-spectroscopy and evaluated the consequences of such phosphorylation. Substitution of these two serines with phosphoserine-mimicking aspartic-acid residues results in a significant increase in helical content, solubility and Ca(2+)-binding capacity above 6 mM [Ca(2+)]. However, neither substitution of Ser(385) nor Ser(393) alone produce any significant changes. Based on the crystal structures of hCASQ2, Ca(2+) binding capacity data, turbidity, and light scattering profiles, it was propose that phosphorylation at these two positions produces a disorder-to-order or coil-to-helix transition of the C-terminus, which in turn provides a more stable network of polyanions. Therefore, considering all the previous reports and the new data, the observed dynamic in vivo phosphorylation of CASQ could provide the basis not only for effective regulation of Ca(2+) buffering capacity, but also for the junctional SR trafficking mechanism.

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Title: Phosphorylation of human calsequestrin: implications for calcium regulation
Creators: Emiliano J Sanchez - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660, USA
Gerhard R Munske
Angela Criswell
Hendrik Milting
A Keith Dunker
Chulhee Kang
Publication Details: Molecular and cellular biochemistry, Vol.353(1-2), pp.195-204
Academic Unit: Chemistry, Department of
Publisher: Netherlands
Identifiers: 99900547236501842
Language: English
Resource Type: Journal article

Phosphorylation of human calsequestrin: implications for calcium regulation

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