| Abstrakt: |
Ribosome hibernation is a key survival strategy bacteria adopt under environmental stress, where a protein, hibernation promotion factor (HPF), transitorily inactivates the ribosome. Mycobacterium tuberculosis encounters hypoxia (low oxygen) as a major stress in the host macrophages, and upregulates the expression of RafH protein, which is crucial for its survival. The RafH, a dual domain HPF, an orthologue of bacterial long HPF (HPFlong), hibernates ribosome in 70S monosome form, whereas in other bacteria, the HPFlong induces 70S ribosome dimerization and hibernates its ribosome in 100S disome form. Here, we report the cryo- EM structure of M. smegmatis, a close homolog of M. tuberculosis, 70S ribosome in complex with the RafH factor at an overall 2.8 Å resolution. The N- terminus domain (NTD) of RafH binds to the decoding center, similarly to HPFlong NTD. In contrast, the C- terminus domain (CTD) of RafH, which is larger than the HPFlong CTD, binds to a distinct site at the platform binding center of the ribosomal small subunit. The two domain-connecting linker regions, which remain mostly disordered in earlier reported HPFlong structures, interact mainly with the anti-Shine Dalgarno sequence of the 16S rRNA. Ribosome hibernation is a key survival strategy bacteria adapt under stress. Here, cryo- EM structure of mycobacterial 70S ribosome with hypoxia stress-induced factor RafH suggests the molecular mechanism of RafH-induced ribosome hibernation. [ABSTRACT FROM AUTHOR] |
Full text from SpringerLink