Is this the future of antibiotics?

A team of ETH Zurich researchers led by professors Nenad Ban and Ruedi Aebersold have studied the highly complex molecular structure of mitoribosomes, which are the ribosomes of mitochondria. Ribosomes are found in the cells of all living organisms. However, higher organisms (eukaryotes), which include fungi, plants, animals and humans, contain much more complex ribosomes than bacteria. In eukaryotes, ribosomes can also be divided into two types: those in the cytosol – which comprises the majority of the cell – and those found in the mitochondria or “power plants” of cells. Mitochondria are only found in eukaryotes.

Ribosomes serve as translation devices for the genetic code and produce proteins based on the information stored in DNA. Every ribosome consists of two subunits. The smaller subunit uses transfer ribonucleic acids (transfer RNA or tRNA) to decode the genetic code it receives in the form of messenger RNA, while the larger subunit joins the amino acids delivered by the transfer RNA together like a string of pearls.

Even higher resolution, even more details

Mitochondrial ribosomes are especially difficult to study because they are found only in small amounts and are difficult to isolate. At the beginning of the year, ETH researchers had shed light on the molecular structure of the large subunit of the mitoribosome in mammalian cells to a resolution of 4.9 Å (less than 0.5 nm). However, this resolution was not adequate to reliably build a complete atomic model of this previously unknown structure. The team lead by ETH Professor Nenad Ban has now succeeded in this task and was able to map the entire structure at a resolution of 3.4 Å (0.34 nm). The researchers recently published their findings in the scientific journal Nature.

The scientists used high-resolution cryo-electron microscopy at the Electron Microscopy Center of ETH Zurich (ScopeM) and state-of-the-art mass spectrometry methods in their experiments. Thanks to recent technical advances in cryo-electron microscopy and the development of direct electron detection cameras that can correct for specimen motion during the exposure, it only recently became possible to capture images of biomolecules at a resolution of less than four angstroms.

Improving the effect of antibiotics

In particular, the new images show the details of the peptidyl transferase centre (PTC), which is where the amino acid building blocks are combined. The proteins synthesised in this way then pass through a tunnel, where they finally exit the large subunit of the ribosome.