# The MmpL3 interactome

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $245,152

## Abstract

ABSTRACT
 Tuberculosis is one of the leading causes of death due to infectious disease despite the availability of anti-
tubercular drugs. The cell envelope of Mycobacterium tuberculosis (Mtb) is notable for the abundance of
mycolic acids (MAs), which are essential to mycobacterial viability. The mycobacterial cell envelope is
extremely hydrophobic, contributes to virulence and antibiotic resistance. Yet, exactly how glycoconjugates
and other species-specific lipids are transported across the inner membrane for cell envelope biosynthesis is
incompletely understood.
 Recent work shows that the Mycobacterial membrane protein Large (MmpL) transporters export lipids
synthesized in the mycobacterial cytoplasm for incorporation into the cell envelope. These transporters are
therefore important for bacterial viability and virulence. MmpL3, the focus of this proposal, is essential and
required for transport of trehalose monomycolate (TMM), the precursor of trehalose dimycolate (TDM) and
mycolyl arabinogalactan peptidoglycan (mAGP). The exact mechanism of MmpL3 export remains elusive.
 RND family proteins typically possess adaptor proteins that assist in substrate transport. As presented in
our preliminary data and recent publication, we identified several lipoproteins that interact with MmpL3 and
MmpL11. We characterized an Mtb lpqN mutant and demonstrated that LpqN has a lipid binding pocket and
interacts with the Ag85 mycolyl transferases. Based on these data, we propose a model where mycobacterial
lipoproteins form a complex with MmpL protein to promote lipid secretion and localization.
 Our hypothesis is that MmpL3 interacts with lipoproteins that facilitate export of TMM and its
incorporation into the cell envelope. The proposed study will combine biochemical and genetic approaches
to identify proteins that complex with MmpL3 to facilitate substrate transport.
 .

## Key facts

- **NIH application ID:** 10496567
- **Project number:** 5R21AI167112-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Georgiana E. Purdy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $245,152
- **Award type:** 5
- **Project period:** 2021-09-27 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496567

## Citation

> US National Institutes of Health, RePORTER application 10496567, The MmpL3 interactome (5R21AI167112-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10496567. Licensed CC0.

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