Journal article
Glycosylation of Skeletal Calsequestrin: IMPLICATIONS FOR ITS FUNCTION
The Journal of biological chemistry, Vol.287(5), pp.3042-3050
01/27/2012
Handle:
https://hdl.handle.net/2376/100939
PMCID: PMC3270961
PMID: 22170046
Abstract
Background:
Calsequestrin serves as a calcium storage/buffer protein in sarcoplasmic reticulum and undergoes a posttranslational modification.
Results:
The specific site, degree, structure, and effects of glycosylation were determined.
Conclusion:
The glycosylation prevented premature polymerization of calsequestrin ensuring mobility to the SR.
Significance:
The glycosylation establishes a functional high capacity calcium binding polymer and allows calsequestrin to be retained in SR.
Calsequestrin (CASQ) serves as a major Ca
2+
storage/buffer protein in the sarcoplasmic reticulum (SR). When purified from skeletal muscle, CASQ1 is obtained in its glycosylated form. Here, we have confirmed the specific site and degree of glycosylation of native rabbit CASQ1 and have investigated its effect on critical properties of CASQ by comparison with the non-glycosylated recombinant form. Based on our comparative approach utilizing crystal structures, Ca
2+
binding capacities, analytical ultracentrifugation, and light-scattering profiles of the native and recombinant rabbit CASQ1, we propose a novel and dynamic role for glycosylation in CASQ. CASQ undergoes a unique degree of mannose trimming as it is trafficked from the proximal endoplasmic reticulum to the SR. The major glycoform of CASQ (GlcNAc
2
Man
9
) found in the proximal endoplasmic reticulum can severely hinder formation of the back-to-back interface, potentially preventing premature Ca
2+
-dependent polymerization of CASQ and ensuring its continuous mobility to the SR. Only trimmed glycans can stabilize both front-to-front and the back-to-back interfaces of CASQ through extensive hydrogen bonding and electrostatic interactions. Therefore, the mature glycoform of CASQ (GlcNAc
2
Man
1–4
) within the SR can be retained upon establishing a functional high capacity Ca
2+
binding polymer. In addition, based on the high resolution structures, we propose a molecular mechanism for the catecholaminergic polymorphic ventricular tachycardia (CPVT2) mutation, K206N.
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Details
- Title
- Glycosylation of Skeletal Calsequestrin
- Creators
- Emiliano J Sanchez - From theKevin M Lewis - theGerhard R Munske - From theMark S Nissen - theChulHee Kang - From the
- Publication Details
- The Journal of biological chemistry, Vol.287(5), pp.3042-3050
- Academic Unit
- Chemistry, Department of
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- T32GM083864; P20RR016454 / National Institutes of Health
- Identifiers
- 99900546547801842
- Language
- English
- Resource Type
- Journal article