The cryo-EM Structure of a Novel 40S Kinetoplastid-Specific Ribosomal Protein
Jailson Brito Querido1, Eder Mancera-Martínez1, Quentin Vicens1
1Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR 9002, 67000 Strasbourg, France.
Abstract:
Kinetoplastids are potentially lethal protozoan pathogens affecting more than 20 million people worldwide. There is a critical need for more specific targets for the development of safer anti-kinetoplastid therapeutic molecules that can replace the scarce and highly cytotoxic current drugs. The kinetoplastid ribosome represents a potential therapeutic target due to its relative structural divergence when compared with its human counterpart. However, several kinetoplastid-specific ribosomal features remain uncharacterized. Here, we present the near-atomic cryoelectron microscopy structure of a novel bona fide kinetoplastid-specific ribosomal (r-) protein (KSRP) bound to the ribosome. KSRP is an essential protein located at the solvent face of the 40S subunit, where it binds and stabilizes kinetoplastid-specific domains of rRNA, suggesting its role in ribosome integrity. KSRP also interacts with the r-protein eS6 at a region that is only conserved in kinetoplastids. The kinetoplastid-specific ribosomal environment of KSRP provides a promising target for the design of safer anti-kinetoplastidian drugs.
Insights
A novel kinetoplastid-specific ribosomal protein (KSRP) was structurally characterized. This protein stabilizes unique kinetoplastid rRNA structures, offering a promising new target for developing safer anti-kinetoplastid drugs.
Area of Science:
- Structural Biology
- Molecular Biology
- Parasitology
Background:
- Kinetoplastids are protozoan pathogens affecting millions globally.
- Current anti-kinetoplastid drugs are scarce and highly cytotoxic.
- There is a critical need for novel therapeutic targets.
Purpose of the Study:
- To characterize the structure of a novel kinetoplastid-specific ribosomal protein (KSRP).
- To investigate KSRP's role in ribosome structure and integrity.
- To identify KSRP as a potential target for new anti-kinetoplastid drugs.
Main Methods:
- Near-atomic cryoelectron microscopy was used to determine the structure of KSRP bound to the kinetoplastid ribosome.
- Biochemical and structural analyses were performed to understand KSRP-rRNA and KSRP-r-protein interactions.
Main Results:
- The near-atomic structure of KSRP bound to the 40S ribosomal subunit was elucidated.
- KSRP is essential and stabilizes kinetoplastid-specific rRNA domains, suggesting a role in ribosome integrity.
- KSRP interacts with r-protein eS6 in a kinetoplastid-conserved region.
Conclusions:
- The kinetoplastid-specific ribosomal protein KSRP is a key component of the kinetoplastid ribosome.
- KSRP's unique structural features and interactions make it a promising target for developing novel anti-kinetoplastid therapeutics.
- Targeting KSRP could lead to safer and more effective drugs against kinetoplastid infections.
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