bacterial lipid transporters
A series of tunnels, bridges, and ferries exist to transport lipids across the periplasm
As drug-resistant strains of pathogenic bacteria are gaining clinical footholds, exploring alternative broad based therapeutic strategies against pathogens is essential. Classically Gram-negative bacteria (such as pathogenic E. coli), are difficult to treat clinically because they contain an outer membrane that serves as a natural barrier against antimicrobials and the immune system. The Mammalian Cell Entry (MCE) protein family, a nearly ubiquitous protein family in double-membraned bacteria, has emerged as a unique class of transporters that facilitate lipid movement between the inner and outer membranes, with implications in building and maintaining the outer membrane. Our lab takes a structure-function based approach to decipher the role of these proteins in double membraned bacteria and organelles. Our structures of MCE proteins from E. coli have revealed diverse architectures that resemble rings, syringes and tunnels.
2D class averages of 7-ring MCE protein LetB (YebT) from Cryo-EM data
Using a structure-driven approach has enabled us to generate hypotheses about the functions of the MCE protein family. We test our models using a combination of biochemistry, biophysics, and bacterial genetics. Currently we are exploring the MCE protein family in different bacterial species with the goal of understanding their role in cell envelope maintenance and pathogenesis.
Questions we are currently addressing include:
1. What is the mechanism of MCE protein-mediated lipid transport?
2. What are the roles of MCE proteins in bacterial cells?