Structural Basis for the C-Terminal Domain of Ribosome Maturation Factor RimM to Bind Ribosomal Protein S19.

Multidrug-resistant tuberculosis (TB) is a serious threat to public health, calling for the development of new anti-TB drugs. Chaperon protein RimM, involved in the assembly of ribosomal protein S19 into 30S ribosomal subunit during ribosome maturation, is a potential drug target for TB treatment. The C-terminal domain (CTD) of RimM is primarily responsible for binding S19. However, both the CTD structure of RimM from (RimM) and the molecular mechanisms underlying RimM binding S19 remain elusive. Here, we report the solution structure, dynamics features of RimM, and its interaction with S19. RimM has a rigid hydrophobic core comprised of a relatively conservative six-strand β-barrel, tailed with a short α-helix and interspersed with flexible loops. Using several biophysical techniques including surface plasmon resonance (SPR) affinity assays, nuclear magnetic resonance (NMR) assays, and molecular docking, we established a structural model of the RimM-S19 complex and indicated that the β4-β5 loop and two nonconserved key residues (D105 and H129) significantly contributed to the unique pattern of RimM binding S19, which might be implicated in a form of orthogonality for species-dependent RimM-S19 interaction. Our study provides the structural basis for RimM binding S19 and is beneficial to the further exploration of RimM as a potential target for the development of new anti-TB drugs.