Tuberculosis is a life-threatening disease that leads to ∼1.5 million annual human deaths, caused by Mycobacterium tuberculosis (Mtb). A common practice to treat this disease is to use antibiotics, half of which target the ribosome. To design ribosome-targeting antibiotics that potently and selectively kill Mtb without affecting the host, researchers need information on the structure of the Mtb ribosome and its unique features to allow specific targeting of the pathogen.
Bio/Bio Prof Junjie Zhang and colleagues used cryo-electron microscopy to solve the structures of the Mtb ribosome that had been difficult to look at by other structural biology methods. This work has been recently published here in Nucleic Acids Research. Collaborating on the project is the Bio/Bio group of Jim Sacchettini. Indeed, many unique features do exist, including some near binding sites for known antibiotics. The most striking of which is a 100-nucleotide long RNA fragment, termed “handle”, which, interestingly, is very flexible in the ribosome. However, flexible parts can be difficult to clearly visualize. In order to see how the handle is moving, Zhang’s group developed a novel method combining several computational techniques to reveal that the handle does not just move flexibly, but also correlatively with other components within the ribosome. These correlated movements suggest roles for the handle in protein translation by the Mtb ribosome.