Structure of a lipid transporter for the bacterial outer membrane
EMSL Project ID
50424
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 unknown how phospholipids are trafficked between the bacterial inner and outer membranes, through the intervening hydrophilic space of the periplasm. Using structure-driven, discovery-based approaches, we recently discovered 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 "bridges" or "pipes" between the inner and outer membrane to facilitate lipid transport (Ekiert, et al. Cell 2017). We are using 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 even transenvelope complexes. 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 the essential process of outer membrane biogenesis. 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.
Project Details
Start Date
2018-11-08
End Date
2019-01-31
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Coudray, Nicolas, Georgia L. Isom, Mark R. MacRae, Mariyah N. Saiduddin, Gira Bhabha, and Damian C. Ekiert. "Structure of bacterial phospholipid transporter MlaFEDB with substrate bound." Elife 9 (2020): e62518.