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

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-04, Vol.11 (4), p.597
• Main Authors: Zhang, Haoran, Zhou, Qiuxiang, Guo, Chenyun, Feng, Liubin, Wang, Huilin, Liao, Xinli, Lin, Donghai
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding Sites; Drug development; Hydrophobicity; Maturation; MD simulation; Molecular Docking Simulation; Molecular modelling; Multidrug resistance; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - metabolism; NMR; NMR spectroscopy; Nuclear magnetic resonance; Plasmids; Protein Binding; Protein Conformation, alpha-Helical; protein dynamics; protein structure; Public health; Ribosomal Proteins - chemistry; Ribosomal Proteins - metabolism; ribosome maturation factor RimM; Spectrum analysis; Surface plasmon resonance; Therapeutic targets; Tuberculosis
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11040597

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.