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Protein complexes involved in building and maintaining the bacterial cell envelope


EMSL Project ID
50674

Abstract

In double-membraned bacteria, the outer membrane forms a barrier between the cell and the outside world, and acts as the first line of defense against the environment. The outer membrane in double-membraned bacterial pathogens protects them against many antibiotics. Therefore, targeting the integrity of the outer membrane is one strategy towards development of new antibiotics against the increasing number of antibiotic-resistant double-membraned (mostly gram-negative) bacteria. Our work is aimed at understanding how the bacterial cell envelope, comprising the inner membrane, outer membrane, and intervening periplasm is built and maintained. In order to build and maintain the outer membrane, cells need to transport phospholipids between the inner and outer membranes, through the hydrophilic periplasm. We recently solved the first structures of a family of proteins called the Mammalian Cell Entry (MCE) proteins, some of which had previously been implicated in lipid transport (Ekiert and Bhabha et al, Cell, 2017). Our structures revealed that these proteins form hexameric channels of varying lengths and architectures, with the potential to transport lipids or other hydrophobic molecules via different mechanisms. We now aim to gain a mechanistic understanding of how these proteins work by a) capturing the MCE proteins in complex with other binding partners b) getting snapshots of the proteins in different functional states (for example, bound to different nucleotides, in the case of MCE transporters that are ATPases) and c) comparing the MCE family of proteins between different double-membraned bacteria.

Project Details

Start Date
2019-01-14
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Gira Bhabha
Institution
New York University School of Medicine

Team Members

Cristina Santarossa
Institution
New York University School of Medicine

Rachel Redler
Institution
New York University School of Medicine

Casey Vieni
Institution
New York University School of Medicine

Harry Scott
Institution
Oregon Health & Science University

Nicolas Coudray
Institution
New York University School of Medicine

Damian Ekiert
Institution
New York University School of Medicine