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β 亚基的 HOOK 结构域通过与质膜静电相互作用来控制电压门控 Ca 通道的门控。

The HOOK region of β subunits controls gating of voltage-gated Ca channels by electrostatically interacting with plasma membrane.

机构信息

a Department of Brain and Cognitive Sciences , DGIST , Daegu , South Korea.

出版信息

Channels (Austin). 2017 Sep 3;11(5):467-475. doi: 10.1080/19336950.2017.1335841. Epub 2017 Jun 1.

DOI:10.1080/19336950.2017.1335841
PMID:28569643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5626366/
Abstract

Recently, we showed that the HOOK region of the β2 subunit electrostatically interacts with the plasma membrane and regulates the current inactivation and phosphatidylinositol 4,5-bisphosphate (PIP) sensitivity of voltage-gated Ca (Ca) 2.2 channels. Here, we report that voltage-dependent gating and current density of the Ca2.2 channels are also regulated by the HOOK region of the β2 subunit. The HOOK region can be divided into 3 domains: S (polyserine), A (polyacidic), and B (polybasic). We found that the A domain shifted the voltage-dependent inactivation and activation of Ca2.2 channels to more hyperpolarized and depolarized voltages, respectively, whereas the B domain evoked these responses in the opposite directions. In addition, the A domain decreased the current density of the Ca2.2 channels, while the B domain increased it. Together, our data demonstrate that the flexible HOOK region of the β2 subunit plays an important role in determining the overall Ca channel gating properties.

摘要

最近,我们发现β2 亚基的 HOOK 区域与质膜静电相互作用,调节电压门控 Ca(Ca)2.2 通道的电流失活和磷脂酰肌醇 4,5-二磷酸(PIP)敏感性。在这里,我们报告说,β2 亚基的 HOOK 区域还调节 Ca2.2 通道的电压依赖性门控和电流密度。HOOK 区域可以分为 3 个结构域:S(多丝氨酸)、A(多酸性)和 B(多碱性)。我们发现 A 结构域分别将 Ca2.2 通道的电压依赖性失活和激活移至更超极化和去极化的电压,而 B 结构域则朝相反的方向引发这些反应。此外,A 结构域降低了 Ca2.2 通道的电流密度,而 B 结构域则增加了电流密度。总之,我们的数据表明β2 亚基的灵活 HOOK 区域在决定整体 Ca 通道门控特性方面起着重要作用。

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2
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Sci Signal. 2016 Jul 5;9(435):ra67. doi: 10.1126/scisignal.aad7247.
3
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Nat Rev Drug Discov. 2016 Jan;15(1):19-34. doi: 10.1038/nrd.2015.5. Epub 2015 Nov 6.
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