Coupling of RYR1 and L-type calcium channels via calmodulin binding domains.
Coupling of RYR1 and L-type calcium channels via calmodulin binding domains.
复制标题
RYR1 和 L 型钙通道通过钙调蛋白结合域偶联。
DOI：
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发表时间：
2001
影响因子：
4.8
通讯作者：
S. Hamilton
中科院分区：
文献类型：
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作者：
S. Sencer;R. Papineni;D. B. Halling;P. Pate;J. Krol;J. Z. Zhang;S. Hamilton
在骨骼肌中，L-型Ca 2+通道直接控制肌浆网Ca 2+释放通道（RYR 1）的开放，而RYR 1反过来又阻止L-型Ca 2+通道失活。我们表明，这两种蛋白质相互作用，使用钙调素结合区域的两种蛋白质。一种代表骨骼肌L型电压依赖性钙通道羧基末端尾的氨基酸1393-1527（D1393-1527）的重组蛋白，结合Ca 2+、Ca 2+钙调蛋白和脱钙钙调蛋白。在不存在钙调蛋白的情况下，D1393-1527与RYR 1和代表RYR 1钙调蛋白结合位点的肽（氨基酸3609-3643）结合。此外，生物素化的R3609-3643肽可与链霉亲和素珠一起使用，从去污剂溶解的横小管膜上拉下[3 H] PN 200 -110标记的L型通道。L-型通道羧基末端尾与RYR 1上的钙调蛋白结合位点的结合可以稳定两种蛋白质之间的接触，为Ca 2+和/或钙调蛋白调节它们的相互作用提供机制，或直接参与这两种蛋白质之间的功能信号传导。这项研究的一个独特方面是发现钙调素结合序列可以作为钙调素以外的蛋白质的特异性结合基序。
In skeletal muscle the L-type Ca2+ channel directly controls the opening of the sarcoplasmic reticulum Ca2+ release channel (RYR1), and RYR1, in turn, prevents L-type Ca2+ channel inactivation. We demonstrate that the two proteins interact using calmodulin binding regions of both proteins. A recombinant protein representing amino acids 1393-1527 (D1393-1527) of the carboxyl-terminal tail of the skeletal muscle L-type voltage-dependent calcium channel binds Ca2+, Ca2+ calmodulin, and apocalmodulin. In the absence of calmodulin, D1393-1527 binds to both RYR1 and a peptide representing the calmodulin binding site of RYR1 (amino acids 3609-3643). In addition, biotinylated R3609-3643 peptide can be used with streptavidin beads to pull down [3H]PN200-110-labeled L-type channels from detergent-solubilized transverse tubule membranes. The binding of the L-type channel carboxyl-terminal tail to the calmodulin binding site on RYR1 may stabilize the contact between the two proteins, provide a mechanism for Ca2+ and/or calmodulin regulation of their interaction, or participate directly in functional signaling between these two proteins. A unique aspect of this study is the finding that calmodulin binding sequences can serve as specific binding motifs for proteins other than calmodulin.