A new study reveals a ‘nano-switch’ in ferredoxin that affects its electron transfer, which could lead to advancements in sensors and drug development.
Researchers in Japan have discovered a mechanism for controlling the potential of an “electron carrier” protein in the redox reaction that all organisms need to obtain energy. Through experiments, the precise 3D structure of the protein, including hydrogen atoms, was determined, and theoretical calculations using this data visualized the electronic structure of the iron-sulfur cluster.
The results revealed, for the first time, that the electric potential of the iron-sulfur cluster changes dramatically depending on the presence or absence of a single hydrogen atom at an amino acid side chain, a so-called “nano-switch” mechanism. This research, recently published in the journal eLife, not only deepens our scientific understanding of biological reactions but also provides crucial insights for the future development of ultra-sensitive sensors for oxygen and nitric oxide, as well as novel drugs.
Unveiling Electron Transfer in Ferredoxin
Most reactions in living organisms involve the “electrons” transfer, called redox reaction. For example, respiration and photosynthesis can be classified as redox reactions. Some proteins that assist in the electron transfer contain irons and sulfurs.
Ferredoxin is a small protein that holds iron-sulfur clusters inside it and is known as the “electron carrier” in living organisms. It is a universal protein thought to be present in almost all living organisms; however, the mechanism by which ferredoxin stably carries electrons has remained a mystery to date.
Breakthroughs in Structural Biology
In this study, the researchers conducted experiments using the Ibaraki Biological Crystal Diffractometer (iBIX) at the Materials and Life Science Experimental Facility (MLF) in the Japan Proton Accelerator Research Complex (J-PARC) and succeeded in determining the precise three-dimensional structure of a ferredoxin at the hydrogen atomic level in experiments using a neutron beam. Visualizing hydrogen atoms in protein molecules using neutrons is extremely difficult, and only less than 0.2% of the entire protein three-dimensional structure database (Protein Data Bank; PDB) has been reported.
Insights into Electron Transfer Mechanisms
Theoretical calculations using experimental geometry, including hydrogen atoms, were performed to elucidate the electronic structure of the iron-sulfur cluster in the ferredoxin. As a result, it was revealed, for the first time, that an amino acid residue (aspartic acid 64) located far from the iron-sulfur cluster has a significant effect on the probability of electron transfer in the iron-sulfur cluster and plays a role like a switch that controls the electron transfer in ferredoxin. Furthermore, it was shown that the mechanism is universal in various organisms.
The results will not only deepen our scientific understanding of biological reactions but also provide a major clue to the future development of ultra-sensitive sensors for oxygen and nitric oxide and novel drugs.
Reference: “Protonation/deprotonation-driven switch for the redox stability of low-potential [4Fe-4S] ferredoxin” by Kei Wada, Kenji Kobayashi, Iori Era, Yusuke Isobe, Taigo Kamimura, Masaki Marukawa, Takayuki Nagae, Kazuki Honjo, Noriko Kaseda, Yumiko Motoyama, Kengo Inoue, Masakazu Sugishima, Katsuhiro Kusaka, Naomine Yano, Keiichi Fukuyama, Masaki Mishima, Yasutaka Kitagawa and Masaki Unno, 9 December 2024, eLife.
DOI: 10.7554/eLife.102506.2
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