1. Redox-Sensitive Cysteines Confer Proximal Control of the Molecular Crowding Barrier in the Nuclear Pore
- Author
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Takahiro K. Fujiwara, Shige H. Yoshimura, Wanzhen Zhang, Ryuji Watanabe, Masahiro Kumeta, and Hide A. Konishi
- Subjects
0301 basic medicine ,genetic structures ,nuclear transport ,Redox ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,molecular crowding ,nuclear pore complex ,medicine ,Humans ,oxidative stress ,Cysteine ,Nuclear membrane ,Nuclear pore ,lcsh:QH301-705.5 ,Barrier function ,Chemistry ,nucleoporin ,Crowding ,030104 developmental biology ,medicine.anatomical_structure ,Förster resonance energy transfer ,lcsh:Biology (General) ,Nuclear Pore ,redox response ,Biophysics ,Nucleoporin ,Nuclear transport ,Oxidation-Reduction ,030217 neurology & neurosurgery - Abstract
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 crowding in vivo that is dynamically regulated at the molecular level., 酸化ストレスが細胞の核膜機能を変える機構を解明 --環境に応じて分子の「混み具合」が変わる仕組み--. 京都大学プレスリリース. 2020-12-16.
- Published
- 2020
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