Mg2+/Ca2+ cation binding cycle of guanylyl cyclase activating proteins (GCAPs): role in regulation of photoreceptor guanylyl cyclase.
Mg2+/Ca2+ cation binding cycle of guanylyl cyclase activating proteins (GCAPs): role in regulation of photoreceptor guanylyl cyclase.
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DOI：
10.1007/s11010-009-0328-6
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发表时间：
2010-01
影响因子：
4.3
通讯作者：
Peshenko, Igor V.
中科院分区：
文献类型：
--
作者：
Dizhoor, Alexander M.;Olshevskaya, Elena V.;Peshenko, Igor V.
光感受器对光子的吸收激活了cGMP的水解，从而关闭了cGMP门控通道，降低了外段的游离钙离子浓度。光抑制钙离子通过cGMP通道的内流，通过鸟苷酸环化酶激活蛋白(GCAPs)激活视网膜鸟苷酸环化酶，从而加速光感受器从兴奋中恢复，恢复其光敏性。GCAP1和GCAP2是脊椎动物中普遍存在的两种GCAPs亚型，它们在杆状反应过程中激活retGC，是EF-Hand超家族中肉豆蔻酰化的钙/镁结合蛋白。它们由一个非金属结合的Ef-Hand结构域和另外三个Ef-Hand结构域组成，每个Ef-Hand结构域都能结合钙和镁。在GCAP1的金属结合Ef-Hand中，不同的点突变可以选择性地阻断Ca~(2+)的结合或同时阻断Ca~(2+)和Mg~(2+)的结合。低Ca~(2+)激活(光适应)或高Ca~(2+)抑制(暗适应)在GCAP中遵循的是Ca~(2+)/Mg~(2+)交换的循环，而不是Ca~(2+)的释放及其与apo-GCAP的结合。在光适应的条件下，EF手中的镁离子结合控制着GCAP1与retGC1的对接，是激活retGC所必需的。C-末端EF-Hand中的镁离子结合既不有助于retGC1与环化酶的对接，也不有助于其在光照下的激活，但在暗适应条件下通过结合钙离子关闭环化酶是特殊需要的。GCAP1和GCA2中的Mg~(2+)/Ca~(2+)交换在不同的细胞内Ca~(2+)浓度范围内工作，在杆状细胞恢复过程中提供了环化酶的两步激活。
Photon absorption by photoreceptors activates hydrolysis of cGMP, which shuts down cGMP-gated channels and decreases free Ca2+ concentrations in outer segment. Suppression of Ca2+ influx through the cGMP channel by light activates retinal guanylyl cyclase through guanylyl cyclase activating proteins (GCAPs) and thus expedites photoreceptors recovery from excitation and restores their light sensitivity. GCAP1 and GCAP2, two ubiquitous among vertebrate species isoforms of GCAPs that activate retGC during rod response to light, are myristoylated Ca2+/Mg2+-binding proteins of the EF-hand superfamily. They consist of one non-metal binding EF-hand-like domain and three other EF-hands, each capable of binding Ca2+ and Mg2+. In the metal binding EF-hands of GCAP1, different point mutations can selectively block binding of Ca2+ or both Ca2+ and Mg2+ altogether. Activation of retGC at low Ca2+ (light adaptation) or its inhibition at high Ca2+ (dark adaptation) follows a cycle of Ca2+/Mg2+ exchange in GCAPs, rather than release of Ca2+ and its binding by apo-GCAPs. The Mg2+ binding in two of the EF-hands controls docking of GCAP1 with retGC1 in the conditions of light adaptation and is essential for activation of retGC. Mg2+ binding in a C-terminal EF-hand contributes to neither retGC1 docking with the cyclase nor its subsequent activation in the light, but is specifically required for switching the cyclase off in the conditions of dark adaptation by binding Ca2+. The Mg2+/Ca2+ exchange in GCAP1 and 2 operates within different range of intracellular Ca2+ concentrations and provides a two-step activation of the cyclase during rod recovery.
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DOI：
10.1085/jgp.106.5.863
发表时间：
1995-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Koutalos Y;Nakatani K;Tamura T;Yau KW
通讯作者：
Yau KW
影响因子：
4.8
作者：
Dizhoor, AM;Hurley, JB
通讯作者：
Hurley, JB
影响因子：
5.5
作者：
Chen, CH;Nakatani, K;Koutalos, Y
通讯作者：
Koutalos, Y
影响因子：
5.5
作者：
HODGKIN, AL;NUNN, BJ
通讯作者：
NUNN, BJ
影响因子：
4.8
作者：
Makino, Clint L.;Peshenko, Igor V.;Dizhoor, Alexander M.
通讯作者：
Dizhoor, Alexander M.