New focus on regulation of the rod photoreceptor phosphodiesterase.

New focus on regulation of the rod photoreceptor phosphodiesterase.
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DOI:
10.1016/j.sbi.2021.03.016
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发表时间:
2021-08
影响因子:
6.8
通讯作者:
Palczewski K
Palczewski K
中科院分区:
生物学2区
文献类型:
--
作者:
Gulati S;Palczewski K

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视杆细胞光感受器磷酸二酯酶(PDE6)是视觉光转导的关键催化酶。PDE6是磷酸二酯酶家族中唯一由PDE6α和PDE6β亚基组成的异二聚体催化核心以及两个抑制性PDE6γ亚基构成的成员。PDE6α和PDE6β都包含两个调节性GAF结构域和一个催化结构域。GAF结构域和紧密结合的PDE6γ亚基与结合GTP的转导素α亚基(Gtα - GTP)协同变构调节催化结构域的活性。近期PDE6αγβγ和PDE6αγβγ - (Gtα - GTP)₂复合物的冷冻电镜结构提供了有价值的信息,进一步阐明了Gtα - GTP对PDE6的变构激活作用。在此我们讨论在对PDE6激活机制的理解方面的最新进展。
Rod photoreceptor phosphodiesterase (PDE6) is the key catalytic enzyme of visual phototransduction. PDE6 is the only member of the phosphodiesterase family that consists of a heterodimeric catalytic core composed of PDE6α and PDE6β subunits and two inhibitory PDE6γ subunits. Both PDE6α and PDE6β contain two regulatory GAF domains and one catalytic domain. GAF domains and the tightly-bound PDE6γ subunits allosterically regulate the activity of the catalytic domain in association with the GTP-bound transducin alpha subunit (Gtα-GTP). Recent cryo-electron microscopy structures of the PDE6αγβγ and PDE6αγβγ-(Gtα-GTP)2 complexes have provided valuable knowledge shedding additional light on allosteric activation of PDE6 by Gtα-GTP. Here we discuss recent developments in our understanding of the mechanism of PDE6 activation.
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