# Physiology of Mycobacterium Tuberculosis with Hibernating Ribosomes

> **NIH NIH R21** · WADSWORTH CENTER · 2020 · $214,140

## Abstract

Project Summary
Bacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-
binding CXXC motif (C+) with their zinc-free (C-) paralogs. Consequence of this process
is generally known to balance zinc homeostasis under depletion of the micronutrient.
Recently, we observed that the C- ribosome in Mycobacterium smegmatis is the
exclusive target of a protein Y homolog, called mycobacterial protein Y (MPY). The cryo-
EM structure reveals that MPY binds to the decoding region of the 30S subunit, thereby
inactivating the ribosome. Moreover, MPY binding is dependent on another
mycobacterial protein, called MPY recruitment factor (MRF), which is induced upon zinc
depletion and interacts with C- ribosomes. Binding of MPY confers structural stability to
C- ribosomes, thereby increasing viability of growth-arrested M. smegmatis under zinc-
limiting conditions. Furthermore expression of C- ribosomes was observed in
Mycobacterium tuberculosis during infection, leading to a hypothesis the zinc-depleted
C- ribosome in the tuberculosis pathogen is also a target of the MPY homologue in this
species. The fundamental implication of our hypothesis is that zinc depletion induces
metabolic dormancy in M. tuberculosis. We will test this hypothesis by determining the
binding of MPY homologue of M. tuberculosis ribosomes produced under zinc starvation
(Aim 1). To obtain a direct correlation between ribosome hibernation and metabolic
dormancy, we will develop a method to visualize ribosome hibernation in live
mycobacterial cells (Aim 2). Together, the proposal will develop a molecular framework
for a long-term investigation on ribosome hibernation and dormancy in M. tuberculosis.

## Key facts

- **NIH application ID:** 9879681
- **Project number:** 5R21AI144474-02
- **Recipient organization:** WADSWORTH CENTER
- **Principal Investigator:** Anil Kumar Ojha
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $214,140
- **Award type:** 5
- **Project period:** 2019-02-22 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9879681

## Citation

> US National Institutes of Health, RePORTER application 9879681, Physiology of Mycobacterium Tuberculosis with Hibernating Ribosomes (5R21AI144474-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9879681. Licensed CC0.

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