Unravelling the assembly of the mitoribosome

A sequential series of auxiliary assembly factors is visualised in action as it assists the small mitoribosomal subunit to form a catalytic complex able to initiate translation of genetic information in human mitochondria.

In recent findings published in Nature, a team of international researchers led by Prof. Alexey Amunts (Stockholm University) used cryo-electron microscopy (cryo-EM) at Diamond’s electron Bio-Imaging Centre (eBIC) to analyse a series of intermediate states in the assembly of the mitroribosome. Cryo-EM permits unique insight into dynamic structural processes, where the team (collecting data remotely) identified eight distinct intermediate states in the multi-step assembly pathway. This included a sequence of assembly factors interacting with each other as an integrated network. Further, the atomic level spatial resolution enabled the discovery of a mitochondria-specific protein which blocks premature binding of genetic material, and also enabled detection of essential structural modifications that occur on the mitoribosomal core at each of the assembly steps.

A platform for new antibiotics

This study identified the chain of events involved in mitoribosome assembly and revealed a new paradigm for a single protein, ms37, linking the assembly to the function of the mitoribosome. The data collected support a unique function for this protein in cell mitochondria. More broadly, this work demonstrates that it is now possible to characterise dynamic processes occuring inside cells, with minimised disruption to the specimen’s native state. Combined with the high spatial resolution achievable using cryo-EM, this opens the door to new avenues for study, for example the visualisation of antibiotics bound to mitoribosomes. This approach could be exploited to determine modifications that induce off-target binding (leading to side effects) and ultimately support the design of more efficient antibiotics.

Remarkably, results showed that the protein mtIF3 (previously known as “initiation" factor) in fact binds during the assembly, and a unique protein mS37 then disrupts its contact. This event marks the completion of the mitoribosome assembly and the initiation of protein synthesis.