# Mechanism of Transport and Folding of Outer Membrane Proteins

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2021 · $304,576

## Abstract

The envelope of Gram-negative bacteria consists of two membranes separated by the
periplasmic compartment that contains the peptidoglycan wall. The inner membrane (IM)
is in contact with the cytosol while the outer membrane (OM) contacts the extracellular
environment. The OM is a unique structure, essential for Gram-negative bacteria,
composed of lipopolysaccharide (LPS), phospholipids and proteins. It is a very selective
permeability barrier that allows the bacteria to survive in hostile environments such as
the gut, where the OM resistance to bile salts allows enteric bacteria to thrive. The
components of the OM are the first to come in contact with a host upon infection and
strongly modulate the interaction of symbiotic and pathogenic bacteria with their host. A
clear understanding of the OM biogenesis process is essential to understand host–
pathogen interactions as well as a fundamental aspect of bacterial physiology.
Outer membrane proteins (OMPs) are integral membrane proteins with b-barrel
structures embedded in the OM. Many OMPs are immunogenic and some of them serve
as adhesins mediating adhesion and colonization of host tissues. OMPs are synthesized
in the cytosol and translocated across the IM by the Sec translocation machinery and
inserted specifically in the outer membrane by a multiprotein complex known as b-Barrel
Assembly Machine (BAM). However, the molecular mechanisms by which OMPs are
targeted to the OM and inserted by BAM are poorly understood.
In this proposal, we will define the fundamentals of OMP transport and assembly
focusing on the BAM complex. We will (i) define the mechanism of OMP targeting to the
OM and (ii) test mechanistic hypotheses of OMP insertion derived from the high-
resolution structures of BAM.

## Key facts

- **NIH application ID:** 10136005
- **Project number:** 5R01GM127462-04
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Marcelo C. Sousa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,576
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136005

## Citation

> US National Institutes of Health, RePORTER application 10136005, Mechanism of Transport and Folding of Outer Membrane Proteins (5R01GM127462-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136005. Licensed CC0.

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