Electron cryo-microscopy visualisation of bioenergetic complexes.
Our research group investigates the fundamental question of how proteins are synthesized, folded and assembled into functional multicomponent membrane complexes that drive the cellular energy production.
Living cells ultimately depend on the conversion of energy derived from foodstuff and light into the chemical form of energy. This crucial bioenergetic step is performed in the membrane systems of mitochondria and chloroplasts. Each one of these organelle types has developed dedicated ribosomes that have diverged from the cytoplasmic counterparts. While mitoribosomes synthesize proteins involved in the oxidative phosphorylation, chlororibosomes produce components driving the pohotosynthetic reactions through pigment-protein units. To dissect the mechanism and dynamics of translation, membrane insertion and bioenergetics in organelles, we use cryo-EM.
Our group determined cryo-EM structures of the human mitoribosome with mRNA, tRNAs and translation activators in 8 different functional states, as well as its assembly intermediates. It revealed unique mechanisms of mRNA binding, tRNA translocation and assembly regulation. We also determined structures of the chlororibosome with translation factors that revealed divarication of the exit tunnel and experimental evidence for convergent evolution of ribosomes from chloroplasts and mitochondria.
These studies showed that protein synthesis machineries in organelles have adopted intricate compositions and unique tasks, adding incredible complexity to the records. The achieved understanding of the architecture of these specialized systems provides now a framework to study even more sophisticated questions regarding the assembly and evolution mechanisms of the critical bioenergetic membranes that fuel life.
Shintaro Aibara, Postdoc
Juni Andréll, Researcher
Yuzuru Itoh, Postdoc
Rasmus Kock Flygaard, Postdoc
Alexander Muhleip, Postdoc
Linnea Axelsson, Student
Annemarie Perez Boerema, Student
Vivek Singh, Student
Victor Tobiasson, Student
Petrov A., Wood E., Bernier C., Norris A., Brown A. and Amunts A. (2018). Structural patching fosters divergence of mitochondrial ribosomes. Molecular Biology and Evolution in press.
Tobiasson V., Dow A., Prisic S. and Amunts A. (2018). Zinc depletion does not necessarily induce ribosome hibernation in mycobacteria. Proc Natl Acad Sci USA in press.
Singh V. and Amunts A. (2018). Application of cryo-EM for visualization of mitoribosomes. Methods in Molecular Biology in press.
Aibara S., Andrell J., Singh V. and Amunts A. (2018). Rapid isolation of the mitoribosome from HEK cells. Journal of visualized experiments 140.
Perez Boerema A., Aibara S., Paul B., Tobiasson V., Kimanius D., Forsberg B. O., Wallden K., Lindahl E. and Amunts A. (2018). Structure of the chloroplast ribosome with chl-RRF and hibernation-promoting factor. Nature Plants 4, 212-217.
Forsberg B. O., Aibara S., Kimanius D., Paul B., Lindahl E. and Amunts A. (2017). Cryo-EM reconstruction of the chlororibosome to 3,2 Å resolution within 24h. International Union of Crystallography journal 4, 723-727.
Brown A., Rathore S., Kimanius D., Aibara S., Bai X., Rorbach J., Amunts A.* and Ramakrishnan V.* (2017). Structures of the human mitochondrial ribosome in native states of assembly. Nature Structural and Molecular Biology 24, 866-869.
Matzov D., Aibara S., Basu A., Zimmerman E., Bashan A., Yap M-N.F., Amunts A.* and Yonath A.* (2017). The cryo-EM structure of hibernating 100S ribosome dimer from pathogenic Staphylococus aureus. Nature comm. 8, 723.
Desai N., Brown A., Amunts A. and Ramakrishnan V. (2017). The structure of the yeast mitochondrial ribosome. Science 355, 528-531.
“Hire very smart people. Leave them alone, but with a tea room to talk. Support them so they have time, & aren’t chasing money.” Max Perutz
If you are interested working in such environment, please contact Alexey Amunts.
Molecular Interactions seminar
Our program for Molecular Interactions brings together researchers focusing on imaging, proteomics and drug discovery. The list of upcoming speakers is found here.
We encourage everyone to take active part.
Sjöstrand Lecture in Structural Biology
The lecture series is set up in the recognition of Fritiof Sjöstrand’s contribution to the development of structural biology.
Jennifer Doudna will give the upcoming Sjöstrand Lecture on the 22ndof August 2019 at 4.00pm in the Biomedicum Lecture Theatre.