Under non-stress conditions, Keap1 grabs cytoprotective transcription factor Nrf2 and represses its activity. Oxidative stresses, sensed by regions inside the large sphere and/or inside the forked stem, allow the translocation of Nrf2 to the nucleus. Nrf2 activates many cytoprotective genes, which protect the cell from damage caused by oxidative stress.
Chikara Sato*, Yutaka Ueno*, Kiyoshi Asai*, Katsutoshi Takahashi², Masahiko Sato³, Andreas Engel§ & Yoshinori Fujiyoshi║
* Supermolecular Science Division, Electrotechnical Laboratory (ETL), Umezono 1-1-4, Tsukuba, 305-8568 Japan ² School of Knowledge Science, Japan Advanced Institute of Science and Technology Hokuriku (JAIST), Asahidai 1-1, Tatsunokuchi, Ishikawa, 923-1211, Japan ³ Central Research Institute, Itoham Foods Inc., Kubogaoka 1-2, Moriya, 302-0104, Japan§Maurice E. MuÈller Institute, at the Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland ║Department of Biophysics, Faculty of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan
Abstract from: Proc Natl Acad Sci U S A. 2010 Jan 27.
Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains.
Voltage-sensitive membrane channels, the sodium channel, the potassium channel and the calcium channel operate together to amplify, transmit and generate electric pulses in higher forms of life. Sodium and calcium channels are involved in cell excitation, neuronal transmission, muscle contraction and many functions that relate directly to human diseases. Sodium channels--glycosylated proteins with a relative molecular mass of about 300,000, are responsible for signal transduction and amplification, and are chief targets of anaesthetic drugs and neurotoxins. Here we present the three-dimensional structure of the voltage-sensitive sodium channel from the eel Electrophorus electricus. The 19 Å structure was determined by helium-cooled cryo-electron microscopy and single-particle image analysis of the solubilized sodium channel. The channel has a bell-shaped outer surface of 135 Å in height and 100 Å in side length at the squareshaped bottom, and a spherical top with a diameter of 65 Å. Several inner cavities are connected to four small holes and eight orifices close to the extracellular and cytoplasmic membrane surfaces. Homologous voltage-sensitive calcium and tetrameric potassium channels, which regulate secretory processes and the membrane potential, may possess a related structure.