Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle.
Characterization of Post-Translational Modifications to Calsequestrins of Cardiac and Skeletal Muscle.
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DOI：
10.3390/ijms17091539
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发表时间：
2016-09-13
影响因子：
5.6
通讯作者：
Kang C
中科院分区：
文献类型：
--
作者：
Lewis KM;Munske GR;Byrd SS;Kang J;Cho HJ;Ríos E;Kang C
集钙蛋白在运输到肌浆网连接部的最终目的地过程中会发生糖基化和磷酸化。为了确定这些翻译后修饰对哺乳动物集钙蛋白的重要性和普遍特征，我们通过质谱法对牛（Bos taurus）、实验小鼠（Mus musculus）和实验大鼠（Rattus norvegicus）的骨骼肌集钙蛋白以及牛、实验大鼠和人的心肌集钙蛋白的糖基化和磷酸化进行了表征。平均而言，骨骼肌集钙蛋白的糖基化由两个N - 乙酰葡糖胺和一个甘露糖（GlcNAc₂Man₁）组成，而心肌集钙蛋白还有另外五个甘露糖（GlcNAc₂Man₆）。骨骼肌集钙蛋白没有磷酸化，而心肌集钙蛋白的C末端尾部含有0到2个磷酸基团，这表明心肌集钙蛋白在体内的磷酸化可能是不均一的。静态光散射实验表明，相对于非糖基化的重组异构体，天然牛骨骼肌集钙蛋白的Ca²⁺依赖性聚合能力有所增强，我们的晶体学研究表明，这可能是由于糖基化为集钙蛋白聚合提供了一个动态的“导轨”样支架。糖基化可能会增强对Ca²⁺浓度变化的聚合/解聚反应，而适当的糖基化反过来又保证了肌浆网对Ca²⁺的有效储存/缓冲以及集钙蛋白（Casq）在其靶位点的定位。
Calsequestrin is glycosylated and phosphorylated during its transit to its final destination in the junctional sarcoplasmic reticulum. To determine the significance and universal profile of these post-translational modifications to mammalian calsequestrin, we characterized, via mass spectrometry, the glycosylation and phosphorylation of skeletal muscle calsequestrin from cattle (B. taurus), lab mice (M. musculus) and lab rats (R. norvegicus) and cardiac muscle calsequestrin from cattle, lab rats and humans. On average, glycosylation of skeletal calsequestrin consisted of two N-acetylglucosamines and one mannose (GlcNAc2Man1), while cardiac calsequestrin had five additional mannoses (GlcNAc2Man6). Skeletal calsequestrin was not phosphorylated, while the C-terminal tails of cardiac calsequestrin contained between zero to two phosphoryls, indicating that phosphorylation of cardiac calsequestrin may be heterogeneous in vivo. Static light scattering experiments showed that the Ca2+-dependent polymerization capabilities of native bovine skeletal calsequestrin are enhanced, relative to the non-glycosylated, recombinant isoform, which our crystallographic studies suggest may be due to glycosylation providing a dynamic “guiderail”-like scaffold for calsequestrin polymerization. Glycosylation likely increases a polymerization/depolymerization response to changing Ca2+ concentrations, and proper glycosylation, in turn, guarantees both effective Ca2+ storage/buffering of the sarcoplasmic reticulum and localization of calsequestrin (Casq) at its target site.
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影响因子：
3.6
作者：
Kim, E;Tam, M;Kang, CH
通讯作者：
Kang, CH
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1016/j.bbamcr.2010.11.009
发表时间：
2011-05-01
影响因子：
5.1
作者：
MacLennan, David H.;Zvaritch, Elena
通讯作者：
Zvaritch, Elena
DOI：
10.1038/nsb0698-409
发表时间：
1998-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
MacLennan, DH;Reithmeier, RAF
通讯作者：
Reithmeier, RAF
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH