Researchers provide high-resolution electron microscopy analysis of the molecular machinery within the respiratory chain.
Oxygen and sugar are the basis of life for animals, plants, fungi and many bacteria. The metabolic process called respiration converts food into energy for cells. The biochemist Prof. Dr. Carola Hunte and her team from the CIBSS Center of Excellence at the University of Friborg have now visualized for the first time with unparalleled precision how an assembly of protein machines, which also provides energy to humans, is structured and functioning. The team studied two respiratory chain complexes fused into a supercomplex in a group of bacteria called Actinobacteria. In addition to providing basic elucidation of respiratory processes, cryogenic electron microscopy analysis could aid in the development of new drugs to treat tuberculosis or diphtheria. “These images are like a journey into our molecular inner workings and its particular rules,” says Hunte, “Elucidating the structure simultaneously sheds light on how the supercomplex works.”
The results of the study are published in the journal Nature Communication and were carried out in collaboration with Dr. Bruno Klaholz, research director at the Center for Integrative Biology (CBI) / Institute of Genetics and Molecular and Cellular Biology (IGBMC) of the CNRS, Inserm and the University of Strasbourg /France.
The energy currency of the cell
Adenosine triphosphate (ATP) is the energy currency of the cell – the molecule is obtained during respiration and transfers energy from food to all processes in the cell. Through the processes of the respiratory chain, adenosine diphosphate is transformed into energy-rich ATP. To do this, the protein complexes of the respiratory chain build up an electrochemical motive force across a membrane with electrons and protons in a complicated physico-chemical process fueled by the combustion of sugar.
“We have analyzed the respiratory cytochrome bcc-aa3 supercomplex. Twenty-six proteins make up the protein machine. The exact interplay of molecular forces and dynamics is not yet well understood, and this is where a description so detailed helps us,” the study explains. first author, Dr. Wei-Chun Kao of Hunte’s team. The complex’s proton pump is very similar to that of humans, the researchers say, but the part where the electrons are taken up by the electron-carrying quinone shows clear differences in the bacteria. “This is where we could bond and develop specific agents that kill pathogenic actinobacteria such as Mycobacterium tuberculosis Where Corynebacterium diphtheriae by interfering with the respiratory chain,” adds Hunte.
Atomic Resolution Cryogenic Microscope
Cryogenic electron microscopy (Cryo-EM) is a technique that examines samples at low temperatures of -183 degrees Celsius in a high-resolution microscope and can resolve structures at the level of single atoms. In the process, machine learning algorithms are used to further refine the collected data. “With these data, we can also better understand the interplay between metabolism and signaling, which is a particular goal of the CIBSS Cluster of Excellence,” Hunte points out. She is a member of the CIBSS Speakers Team, which develops integrative approaches to biological signaling research. The cryo-EM measurements took place at the CBI/IGBMC in Strasbourg/Illkirch. The Freiburg Research Collaboration Program of FRIAS — Institute for Advanced Study Friborg supported this international collaboration.
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