Journal article
High-capacity Ca2+ Binding of Human Skeletal Calsequestrin
The Journal of biological chemistry, Vol.287(14), pp.11592-11601
03/30/2012
Handle:
https://hdl.handle.net/2376/115507
PMCID: PMC3322862
PMID: 22337878
Abstract
Background:
Calsequestrin is a calcium storage/buffer protein within the sarcoplasmic reticulum and binds large amounts of Ca
2+
in a unique manner.
Results:
The specific coordination, geometry, and cooperative effects of Ca
2+
binding were determined.
Conclusion:
The oligomeric state of calsequestrin is directly related to high-capacity Ca
2+
binding.
Significance:
This is the first report of specific Ca
2+
coordination sites in calsequestrin and provides a pathological link to related disorders.
Calsequestrin, the major calcium storage protein in both cardiac and skeletal muscle, binds large amounts of Ca
2+
in the sarcoplasmic reticulum and releases them during muscle contraction. For the first time, the crystal structures of Ca
2+
complexes for both human (hCASQ1) and rabbit (rCASQ1) skeletal calsequestrin were determined, clearly defining their Ca
2+
sequestration capabilities through resolution of high- and low-affinity Ca
2+
-binding sites. rCASQ1 crystallized in low CaCl
2
buffer reveals three high-affinity Ca
2+
sites with trigonal bipyramidal, octahedral, and pentagonal bipyramidal coordination geometries, along with three low-affinity Ca
2+
sites. hCASQ1 crystallized in high CaCl
2
shows 15 Ca
2+
ions, including the six Ca
2+
ions in rCASQ1. Most of the low-affinity sites, some of which are μ-carboxylate-bridged, are established by the rotation of dimer interfaces, indicating cooperative Ca
2+
binding that is consistent with our atomic absorption spectroscopic data. On the basis of these findings, we propose a mechanism for the observed
in vitro
and
in vivo
dynamic high-capacity and low-affinity Ca
2+
-binding activity of calsequestrin.
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Details
- Title
- High-capacity Ca2+ Binding of Human Skeletal Calsequestrin
- Creators
- Emiliano J Sanchez - From theKevin M Lewis - Department of Chemistry, Washington State University, Pullman, Washington 99164Benjamin R Danna - From theChulHee Kang - From the
- Publication Details
- The Journal of biological chemistry, Vol.287(14), pp.11592-11601
- Academic Unit
- Chemistry, Department of
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Identifiers
- 99900548301601842
- Language
- English
- Resource Type
- Journal article