Thermodynamic linkage between calmodulin domains binding calcium and contiguous sites in the C-terminal tail of Ca(V)1.2.
Thermodynamic linkage between calmodulin domains binding calcium and contiguous sites in the C-terminal tail of Ca(V)1.2.
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DOI：
10.1016/j.bpc.2011.06.007
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Shea MA
中科院分区：
文献类型：
--
作者：
Evans TI;Hell JW;Shea MA
钙调素（CaM）与心脏L型钙通道（CaV1.2）的细胞内C末端尾（CTT）结合，通过识别有助于通道关闭的负反馈机制的位点来调节Ca 2+内流。CaM在低静息[Ca 2 +]下与CaV 1.2缔合，但当细胞内[Ca 2 +]升高时，CaM准备改变构象和位置。CaM结合Ca ~（2+）和CaM结合CTT的结构域是相互联系的热力学函数。为了更好地理解调控，我们确定了CaM结构域与代表前IQ位点A1588和C1614的肽结合的能量学，以及作为重叠肽IQ 1644和IQ′1650研究的IQ基序，以及它们对钙结合的影响。(Ca2+）4-CaM非常有利地结合所有四种肽（Kd ≤ 2 nM）。连锁分析显示IQ 1644 -1670以约1 pM的Kd结合。在前IQ区，（Ca ~（2+））2-N-结构域优先与A1588结合，而（Ca ~（2+））2-C-结构域优先与C1614结合。当与C1614结合时，N-结构域中的钙结合影响C-结构域的三级构象。基于热力学，我们提出了钙依赖性构象变化的结构机制，其中CTT位点A和C之间的连接体形成A-C发夹，该发夹由钙饱和的CaM桥接。
Calmodulin (CaM) binding to the intracellular C-terminal tail (CTT) of the cardiac L-type Ca2+ channel (CaV1.2) regulates Ca2+ entry by recognizing sites that contribute to negative feedback mechanisms for channel closing. CaM associates with CaV1.2 under low resting [Ca2+], but is poised to change conformation and position when intracellular [Ca2+] rises. CaM binding Ca2+, and the domains of CaM binding the CTT are linked thermodynamic functions. To better understand regulation, we determined the energetics of CaM domains binding to peptides representing pre-IQ sites A1588, and C1614 and the IQ motif studied as overlapping peptides IQ1644 and IQ′1650 as well as their effect on calcium binding. (Ca2+)4-CaM bound to all four peptides very favorably (Kd ≤ 2 nM). Linkage analysis showed that IQ1644–1670 bound with a Kd ~1 pM. In the pre-IQ region, (Ca2+)2-N-domain bound preferentially to A1588, while (Ca2+)2-C-domain preferred C1614. When bound to C1614, calcium binding in the N-domain affected the tertiary conformation of the C-domain. Based on the thermodynamics, we propose a structural mechanism for calcium-dependent conformational change in which the linker between CTT sites A and C buckles to form an A-C hairpin that is bridged by calcium-saturated CaM.
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影响因子：
5.7
作者：
Feldkamp, Michael D.;Yu, Liping;Shea, Madeline A.
通讯作者：
Shea, Madeline A.
DOI：
10.1016/j.bbrc.2006.12.070
发表时间：
2007-02-16
影响因子：
3.1
作者：
Lian, Lu-Yun;Myatt, Daniel;Kitmitto, Ashraf
通讯作者：
Kitmitto, Ashraf
CAMKII将Ca2+通道的camkii tethers建立，建立了Ca2+信号的本地和专用集成商进行便利。
影响因子：
7.8
作者：
Hudmon, A;Schulman, H;Kim, J;Maltez, JM;Tsien, RW;Pitt, GS
通讯作者：
Pitt, GS
DOI：
10.1016/j.str.2008.07.010
发表时间：
2008-10-08
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Kim EY;Rumpf CH;Fujiwara Y;Cooley ES;Van Petegem F;Minor DL Jr
通讯作者：
Minor DL Jr
影响因子：
5.7
作者：
Fallon, JL;Halling, DB;Quiocho, FA
通讯作者：
Quiocho, FA