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Published on: May 19, 2017
High-capacity Ca2+ binding of human skeletal calsequestrin
Emiliano J Sanchez1, Kevin M Lewis, Benjamin R Danna
1School of Molecular Biosciences, Washington State University, Pullman, Washington 99164, USA.
The Journal of Biological Chemistry
|February 17, 2012
Summary
Calsequestrin (CASQ) protein crystal structures reveal detailed Ca(2+) binding sites. This provides new insights into the dynamic, high-capacity calcium storage crucial for muscle contraction.
Area of Science:
- Biochemistry
- Structural Biology
- Muscle Physiology
Background:
- Calsequestrin (CASQ) is the primary intracellular calcium (Ca2+) storage protein in muscle sarcoplasmic reticulum.
- CASQ plays a critical role in regulating muscle contraction by binding and releasing Ca2+.
Purpose of the Study:
- To determine the crystal structures of Ca2+ complexes for human (hCASQ1) and rabbit (rCASQ1) skeletal calsequestrin.
- To elucidate the Ca2+ sequestration capabilities and binding sites within skeletal calsequestrin.
Main Methods:
- X-ray crystallography was used to determine the structures of rCASQ1 and hCASQ1 in complex with Ca2+.
- Atomic absorption spectroscopy was employed to validate Ca2+ binding properties.
Main Results:
- Three high-affinity Ca2+ sites with distinct coordination geometries and three low-affinity sites were identified in rCASQ1.
- hCASQ1 structures revealed 15 Ca2+ ions, including those found in rCASQ1.
- Cooperative Ca2+ binding, mediated by dimer interface rotation and μ-carboxylate bridges, was observed in low-affinity sites.
Conclusions:
- The determined structures provide a detailed atomic-level understanding of calsequestrin's Ca2+ binding sites.
- A mechanism for the dynamic, high-capacity, low-affinity Ca2+ binding of calsequestrin is proposed.
- These findings enhance our comprehension of calcium homeostasis in muscle function.
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