Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling.
Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling.
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DOI：
10.1016/j.jmb.2014.07.033
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发表时间：
2014-11-11
影响因子：
5.6
通讯作者：
Chu, Feixia
中科院分区：
文献类型：
--
作者：
Zeng-Elmore, Xiaohui;Gao, Xiong-Zhuo;Pellarin, Riccardo;Schneidman-Duhovny, Dina;Zhang, Xiu-Jun;Kozacka, Katie A.;Tang, Yang;Sali, Andrej;Chalkley, Robert J.;Cote, Rick H.;Chu, Feixia
关键词：
光感受器磷酸二酯酶 (PDE6) 是视杆细胞和视锥细胞光感受器视觉激发通路中的中心效应酶。它的严格调节对于视觉检测的速度、灵敏度、恢复和适应至关重要。尽管 PDE6 激活/失活途径的主要步骤已被确定，但由于缺乏对 PDE6 全酶 (αβγγ) 分子组织的了解，对 PDE6 调节的机制理解受到限制。在这里，我们主要基于化学交联和质谱分析，通过 PDE6 催化二聚体 (αβ) 的综合结构测定来表征 PDE6 全酶。我们根据高密度交联数据构建的模型阐明了两个催化亚基的平行组织，在串联调节 GAF 域内并置 α 螺旋片段，为二聚化提供多个位点。与 apo 状态下的 PDE2 结构相比，这两个催化结构域以开放构型存在。揭示了 γ 亚基与 α 和 β 亚基的 GAFa 结构域差异结合的详细结构元件，从而深入了解 PDE6 激活/失活循环的调节。
Photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in visual excitation pathway in rod and cone photoreceptors. Its tight regulation is essential for the speed, sensitivity, recovery and adaptation of visual detection. Although major steps in the PDE6 activation/deactivation pathway have been identified, mechanistic understanding of PDE6 regulation is limited by the lack of knowledge about the molecular organization of the PDE6 holoenzyme (αβγγ). Here, we characterize the PDE6 holoenzyme by integrative structural determination of the PDE6 catalytic dimer (αβ), based primarily on chemical cross-linking and mass spectrometric analysis. Our models built from the high-density cross-linking data elucidate a parallel organization of the two catalytic subunits, with juxtaposed α-helical segments within the tandem regulatory GAF domains to provide multiple sites for dimerization. The two catalytic domains exist in an open configuration when compared to the structure of PDE2 in the apo state. Detailed structural elements for a differential binding of the γ-subunit to the GAFa domains of the α- and β-subunit are revealed, providing insight into the regulation of the PDE6 activation/deactivation cycle.
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影响因子：
4.8
作者：
Guo, Lian-Wang;Muradov, Hakim;Ruoho, Arnold E.
通讯作者：
Ruoho, Arnold E.
DOI：
10.1073/pnas.93.11.5407
发表时间：
1996-05-28
影响因子：
11.1
作者：
Artemyev, NO;Natochin, M;Hamm, HE
通讯作者：
Hamm, HE
影响因子：
4.8
作者：
Muradov, KG;Boyd, KK;Artemyev, NO
通讯作者：
Artemyev, NO
影响因子：
4.1
作者：
ARTEMYEV, NO;HAMM, HE
通讯作者：
HAMM, HE
DOI：
10.1073/pnas.91.11.4845
发表时间：
1994-05-24
影响因子：
11.1
作者：
COTE, RH;BOWNDS, MD;ARSHAVSKY, VY
通讯作者：
ARSHAVSKY, VY