Redox-Sensitive Cysteines Confer Proximal Control of the Molecular Crowding Barrier in the Nuclear Pore
Redox-Sensitive Cysteines Confer Proximal Control of the Molecular Crowding Barrier in the Nuclear Pore
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DOI：
10.1016/j.celrep.2020.108484
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发表时间：
2020-12-15
期刊：
影响因子：
8.8
通讯作者：
Kumeta，Masahiro
中科院分区：
文献类型：
--
作者：
Zhang，Wanzhen;Watanabe，Ryuji;Kumeta，Masahiro
核孔复合体与核膜上本质上无序的区域形成高度拥挤的选择性屏障，以协调核细胞质分子通讯。尽管已知氧化应激会改变屏障功能，但这种核孔复合物适应性控制的分子机制仍然未知。在这里，我们揭示了响应各种氧化还原环境对核孔内拥挤势垒的系统控制。使用拥挤敏感的 FRET（福斯特共振能量转移）探针直接测量拥挤状态，揭示了核孔亚基的特定作用，这些亚基通过适应性地形成或破坏氧化还原敏感的二硫键来调整拥挤程度，以响应不同的氧化还原条件。通过核运输的单分子荧光测量研究了拥挤控制与核孔屏障功能之间的关系。基于这些发现，我们提出了一种在分子水平上动态调节的体内分子拥挤的近端控制模型。
The nuclear pore complex forms a highly crowded selective barrier with intrinsically disordered regions at the nuclear membrane to coordinate nucleocytoplasmic molecular communications. Although oxidative stress is known to alter the barrier function, the molecular mechanism underlying this adaptive control of the nuclear pore complex remains unknown. Here we uncover a systematic control of the crowding barrier within the nuclear pore in response to various redox environments. Direct measurements of the crowding states using a crowding-sensitive FRET (Förster resonance energy transfer) probe reveal specific roles of the nuclear pore subunits that adjust the degree of crowding in response to different redox conditions, by adaptively forming or disrupting redox-sensitive disulfide bonds. Relationships between crowding control and the barrier function of the nuclear pore are investigated by single-molecular fluorescence measurements of nuclear transport. Based on these findings, we propose a proximal control model of molecular crowdingin vivothat is dynamically regulated at the molecular level.