The ribosomal maturation factor P from Mycobacterium smegmatis facilitates the ribosomal biogenesis by binding to the small ribosomal protein S12.

Abstract

The ribosomal maturation factor P (RimP) is a highly conserved protein in bacteria and has been shown to be important in ribosomal assembly in Escherichia coli Because of its central importance in bacterial metabolism, RimP represents a good potential target for drug design to combat human pathogens such as Mycobacterium tuberculosis However, to date, the only RimP structure available is the NMR structure of the ortholog in another bacterial pathogen, Streptococcus pneumoniae Here, we report a 2.2 Å resolution crystal structure of MSMEG_2624, the RimP ortholog in the close M. tuberculosis relative Mycobacterium smegmatis, and using in vitro binding assays, we show that MSMEG_2624 interacts with the small ribosomal protein S12, also known as RpsL. Further analyses revealed that the conserved residues in the linker region between the N- and C-terminal domains of MSMEG_2624 are essential for binding to RpsL. However, neither of the two domains alone was sufficient to form strong interactions with RpsL. More importantly, the linker region was essential for in vivo ribosomal biogenesis. Our study provides critical mechanistic insights into the role of RimP in ribosome biogenesis. We anticipate that the MSMEG_2624 crystal structure has the potential to be used for drug design to manage M. tuberculosis infections.

• Authors: Tinyi Chu, Xing Weng, Carmen Oi Kwan Law, Hoi-Kuan Kong, Jeffrey Lau, Sheila Li, Hoa Quynh Pham, Rui Wang, Liang Zhang, Richard Y T Kao, Kwok-Fai Lau, Jacky Chi Ki Ngo, Terrence Chi Kong Lau
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 294 Issue 1 Pg. 372-378 (01 04 2019) ISSN: 1083-351X [Electronic] United States
• PMID: 30409901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Chu et al.

Chemical References

• Bacterial Proteins
• Escherichia coli Proteins
• Ribosomal Protein S9
• Ribosomal Proteins
• RpsI protein, E coli

Topics

• Bacterial Proteins (chemistry, metabolism)
• Crystallography, X-Ray
• Escherichia coli Proteins
• Mycobacterium smegmatis (chemistry, metabolism)
• Protein Binding
• Protein Domains
• Ribosomal Protein S9
• Ribosomal Proteins (biosynthesis, chemistry)
• Ribosomes (chemistry, metabolism)
• Streptococcus pneumoniae (chemistry, metabolism)