IMAGE: The mitoribosome is attached to its organ transducer because it undergoes synthesis of bioenergetic proteins (yellow glow). view more
Credit: Dan W. Nowakowski and Alexey Amunts
Scientists are discovering for the first time how the body’s energy makers are fabricated using eBIC’s Cryo-Electron Microscopy (cryo-EM) inside a Diamond that is based in Oxfordshire.
New paper published in Science today (19 February 2021) with an international team of researchers reporting a view of the molecular mechanism of protein synthesis by organs in mitochondria. This is a fundamental new understanding of how the human mitoribosome works and could explain how mutations and deregulation lead to disorders such as deafness and disease leading to the development of cancer.
Mitochondria are intracellular organs that are small but strong power centers in our body. They use oxygen that we take in and come from foods we eat to produce more than 90% of our energy, thus effectively supporting our lives. . Mitochondria are especially important in high energy organs such as heart, liver, muscles and brain. For example, nearly 40% of all heart muscle cells are made up of mitochondria.
Most energy production in mitochondria occurs in naturally grown nano-factors embedded in a specific membrane. These nano-factories include proteins that collect ions and electrons collaboratively to generate our body’s chemical energy money that needs to be maintained, replaced and replaced. doubled during cell division. To address this, mitochondria have their own protein-making mechanism called the mitoribosome. The first basic understanding of what the mitoribosome looks like was completed in 2014.
“7 years ago, our work on the mitoribosome from yeast was named the Revolution Resolution. The current study represents a further development than the first break. Not only does it appear as the human mitoribosome is designed at an unprecedented level of precision, but it also defines the molecular mechanism that will direct the bioenergetics process to fuel life, ”said lead author Alexey Amunts, Head of the program for the Biology of Molecular Interactions, at SciLifeLab in Sweden.
The term Resolution Revolution was coined at Science journal regarding the first successful structure determination of the mitoribosome. This represented a methodological innovation in the application of cryo-EM to understand molecular structures. However, this first view of the architecture revealed only part of a picture of a static model. Nevertheless the mitoribosome is a flexible molecular device that needs to move its components relative to each other in order to function. Thus, in the current study, the high-throughput cryo-EM data acquisition team at Diamond Biomass Imaging Center (eBIC) at Diamond obtained an additional 30 hours of data that allowed the team to report conformal changes during protein synthesis process and connection to the membrane adapter. EBIC has been a strategic investment from the Wellcome Trust, BBSRC UKRI and MRC. Being rooted in Diamond, eBIC benefits among other things the established user support.
“Our study revealed the dynamic molecular apparatus that explains how the mitoribosome works to create the cell powerhouse and shows that the mitoribosome is much more flexible and functional than previously thought. detection of genital conformal changes represents a disabling gateway of the mitoribosome in bacterial and cytosolic systems. Together, the data offer a molecular view of how proteins are synthesized in human mitochondria, “Alexey Amunts adds.
Yuriy Chaban, eBIC Chief Microscopy Electron Scientist, Diamond ideas; “At Diamond, we are pushing the limits of what can be measured in the physical and life sciences and this latest development is an honor for the team who are consistently involved in what can be achieved.
The most important feature of Alexey’s work is the interaction between mitoribosome and OXA1L and the flexibility associated with it. The fact that such a flexible mitoribosome is not new, but the specific flexibility is related to the OXA1L interaction. This is important for the synthesis of member proteins, including respiratory chain proteins. Overall, this work greatly expands our understanding of how the mitoribosome works. The work by Alexey Amunts lab solves another mystery about basic biological processes necessary to create life as we know it. ”
The sequencing of the human mitochondrial genome 40 years ago was a turning point in mitochondrial research, posting a specific putative mechanism for the synthesis of the mitochondrial transmembrane proteins. In fact, the detected gating mechanism of the human mitoribosome represents a unique event. Thus, the structural data offer a basic understanding of how bioenergetic proteins are synthesized by our body.
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Paper: MITORIBOSOME Mechanism of mitochondrial protein synthesis by membrane – science.sciencemag.org/content/ DOI 10.1126 / science.abe0763
Authors / Resources: Yuzuru Itoh1,2 *, Juni Andréll1,2 *, Austin Choi3 *, Uwe Richter4,5 *, Priyanka Maiti3, Robert B. Best6, Antoni Barrientos3, Brendan J. Battersby4, Alexey Amunts1,2
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Sweden. 2Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. 3rd Department of Neurology, Miami Miller University School of Medicine, Miami, USA. 4 Institute of Biotechnology, University of Helsinki, Finland. 5 University of Newcastle, Newcastle upon Tyne, UK. 6 Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
About eBIC and the Diamond Light Source: http: // www.
The Center for Electron Biometrics (eBIC) provides scientists in the field of cryo-electron microscope with state-of-the-art experimental equipment and knowledge for single-particle analysis, cryo-tomography and microcrystalline electron differentiation. . Currently there are five Titan Krios microscopes, Talos Arctica, two Glacios, and cryo-FIB / SEM Scios and Aquilos; EBIC is also home to Leica cryo-CLEM for light correlation studies and electron microscopy.
The location of eBIC next to Diamond beamlines, the Laser Central Facility, the Harwell Research Center and the Rosalind Franklin Institute allows scientists to combine cryo-electron microscopy with many other modern techniques.
EBIC was set up at Diamond after a £ 15.6 million grant from the Wellcome Trust, the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC).
Diamond Light Source provides communities of business and academic users with state-of-the-art research tools to enable world-changing science. Shaped like a giant ring, it acts like a giant microscope, accelerating electricity to distances close to light, to produce light 10 billion times brighter than the Sun, which is then directed to 33 a laboratory called beamlines. In addition to those, Diamond offers access to several integrated laboratories including the state-of-the-art Electron Biomaging Center (eBIC) and the Electron Physical Science Imaging Center (ePSIC).
Diamond serves as a change agent, tackling 21st century challenges such as disease, clean energy, food security and more. Since operations began, more than 14,000 researchers from both academia and industry have used Diamond to conduct experiments, supported by around 700 world-class workers. More than 8,000 scientific articles have been published by our users and scientists.
Funded by the UK Government through the Science and Technology Resources Council (SCFC), and by the Wellcome Trust, Diamond is one of the most advanced scientific resources in the world, and its advanced capabilities help to keeping the UK at the forefront of science. research.
SciLifeLab. (Science for Life Laboratory) is a collaborative center for the leading research centers in Sweden, providing the largest life sciences infrastructure in the country. It is a joint venture of Swedish universities that aims to address technologies to the academic community and develop advanced research. More information about Alexey Amunts and his teams working on his webpage https: /