# Dissecting the structure, function, and mechanisms of diverse protein-based metabolic organelles in bacteria

> **NIH NIH R01** · IOWA STATE UNIVERSITY · 2020 · $588,223

## Abstract

Abstract/Summary:
Bacterial microcompartments (MCPs) are giant protein assemblies that serve as metabolic organelles in diverse bacteria
found throughout the microbial world. These extraordinary structures are composed of thousands of subunits that assemble
to form a polyhedral outer shell encapsulating a series of sequentially acting metabolic enzymes. MCPs typically
encapsulate pathways that produce volatile or toxic intermediates that must be confined and metabolized to other compounds
before diffusing out of the MCP and into the bacterial cytosol. MCPs confer special growth advantages to enteric bacteria
and are linked to bacterial pathogenesis and the dissemination of enteric pathogens. Prior studies have focused primarily
on selected MCP types, and important advances have been made. However, a number of mechanistic questions remain
unanswered and some important MCP types are essentially uncharacterized. Prior work by our dual-PI team (Bobik and
Yeates) focused primarily on the propanediol utilization (Pdu) MCP, which is used by Salmonella and other enteric bacteria
to degrade 1,2-propanediol while sequestering a toxic intermediate, propionaldehyde. Our research in the previous cycle
led to numerous important discoveries and critical insights into mechanistic aspects of how the Pdu MCP functions. Our
key findings cover biological phenomena related to protein structure and assembly, molecular recognition, molecular
transport, and molecular evolution. Our current proposal focuses on (1) remaining questions about the assembly and
operation of the Pdu MCP of Salmonella, and (2) early-stage investigations into a new and diverse class of MCPs (which
we identified bioinformatically) whose key internalized enzymes catalyze glycyl-radical-based reactions. Our continuing
work on the Pdu MCP will answer outstanding questions about protein-protein interactions used to guide the assembly of
the Pdu MCP– our earlier work led to the discovery of peptide targeting sequences that direct enzyme encapsulation by
binding the interior surface of MCP shells. However, further experiments are required to paint a clearer picture about
preferential associations by varied targeting sequences and their contribution to higher-order structural organization. In
prior work, we also showed that pores through the shell proteins in the Pdu MCP have evolved for selective diffusive
molecular transport of small molecules. In our continuing work, we propose experiments to investigate the dynamics and
regulation of protein conformational changes that affect pore opening and closing in MCP shell proteins. The second part
of the proposal focuses on the newly-defined and little-studied class of MCPs that encapsulate metabolic pathways
dependent on glycyl-radical (Gr) enzymes. A number of Gr-MCPs are found in bacteria that inhabit the large intestine and
which can infect the urinary tract. We will undertake work on three proposed Gr subtypes: one type that metabolizes 1,2-
PD (similar...

## Key facts

- **NIH application ID:** 9916683
- **Project number:** 5R01AI081146-11
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** THOMAS Aquinas BOBIK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $588,223
- **Award type:** 5
- **Project period:** 2009-07-17 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916683

## Citation

> US National Institutes of Health, RePORTER application 9916683, Dissecting the structure, function, and mechanisms of diverse protein-based metabolic organelles in bacteria (5R01AI081146-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9916683. Licensed CC0.

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