# Structural characterization of MCE mediated lipid transport across the Mycobacterial cell envelope

> **NIH NIH F30** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $50,520

## Abstract

PROJECT SUMMARY / ABSTRACT:
 The cell envelope of Mycobacterium tuberculosis (Mtb) serves an important role as protection against
common antimicrobials and host cell defenses, but also a barrier through which Mtb must transport host
derived nutrients. The MCE protein family (originally implicated in Mammalian Cell Entry) is nearly ubiquitous in
double-membraned bacteria, and MCE proteins are now believed to act as transporters that facilitate lipid
movement between the inner and outer membranes. While Mtb MCE proteins are critical for virulence, their
mechanism in Mtb remains unclear. Due to Mtb’s distinct cell envelope Mtb MCE proteins likely adopt a unique
architecture to mediate transport. In addition, throughout the course of Mtb infection MCE transporters are
believed to be differentially expressed by MCE transcriptional regulators (MceRs). This suggests that
environmental sensing in Mycobacteria in turn alters transcription of the mce operons. Using structural biology,
biochemistry, and genetic complementation assays, I will provide the first glimpse into the architecture of Mtb
Mce protein systems and elucidate how MceRs interact with their operator sequences at the molecular level to
regulate mce operons. To do so I propose the following aims: (Aim 1) structure determination of the Mce4 lipid
transport system from Mycobacterium smegmatis and (Aim 2) structural characterization and DNA-binding
specificity of MceRs. My work will provide the first glimpse at the architecture of the M. smegmatis Mce4
transporter system, as well as the molecular mechanisms of MceR mediated mce operon regulation, which
may shed light on the mechanisms of cell envelope maintenance in Mtb and provide a novel target for
therapeutics.

## Key facts

- **NIH application ID:** 10068459
- **Project number:** 1F30AI154907-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Casey Vieni
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068459

## Citation

> US National Institutes of Health, RePORTER application 10068459, Structural characterization of MCE mediated lipid transport across the Mycobacterial cell envelope (1F30AI154907-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10068459. Licensed CC0.

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