# Structure and function of MCE systems in bacteria

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2024 · $421,656

## Abstract

PROJECT ABSTRACT
The bacterial outer membrane is a lipid bilayer that plays a key role in resistance to antibiotics, detergents, and
other external stresses. Despite decades of research on the bacterial envelope, it is still unclear how
phospholipids are trafficked between the bacterial inner and outer membranes. In addition, many other kinds of
hydrophobic molecules must be imported or exported from the cell, and dedicated transport systems are
required to move many of these molecules across the aqueous periplasm and outer membrane. Research in
my lab focuses on studying transport mechanisms in the bacterial cell envelope. We have shown that members
of the mammalian cell entry (MCE) protein family form structurally diverse hexameric rings and barrels, and
that some of these proteins may form tunnels between the inner and outer membrane to facilitate lipid
transport. Very recently, several studies of the Mla pathway have been published by our lab and others, leading
to mechanistic insights into how this pathway may transport lipids across the cell envelope. Several other
MCE systems remain largely uncharacterized, and our initial work suggests that these function by
fundamentally different mechanisms relative to the Mla pathway. In the future, we will work to understand how
these unexplored MCE transport systems drive the transport of a range of hydrophobic substrates across the
cell envelope. We will use cryo-EM and X-ray crystallography to unravel how the structure of the individual
components supports their biological functions, and how these components assemble into larger inner
membrane, outer membrane, and potentially transenvelope complexes. We will also employ complementary
genetic and biochemical approaches to test hypotheses and probe the mechanism of trafficking by MCE
systems, including the identification of transporter substrates, how transport activity is regulated, how
lipids/substrates are are extracted from and inserted into the inner and outer membranes, and how
lipids/substrates are transported across the periplasm. This work will advance our understanding of a
fundamental yet poorly understood aspect of bacterial cell biology, and may open up avenues to the
development of new antibiotics that target important cellular processes. In addition, the presence of MCE
proteins in some double-membraned organelles, such as chloroplasts, suggests that understanding E. coli
MCE systems will also have direct implications for lipid trafficking in other bacterial-derived organelles.

## Key facts

- **NIH application ID:** 10892786
- **Project number:** 5R35GM128777-08
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Damian Charles Ekiert
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $421,656
- **Award type:** 5
- **Project period:** 2018-08-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892786

## Citation

> US National Institutes of Health, RePORTER application 10892786, Structure and function of MCE systems in bacteria (5R35GM128777-08). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10892786. Licensed CC0.

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