Research Seminar: Rethinking the Mla pathway: Evidence for lipid transport towards the outer membrane in Gram-negative bacteria 

Dr. Tim Knowles,  School of Biosciences, University of Birmingham

Tuesday 12th June, 1.00 p.m., Stacey Lecture Theatre 1

The Mla pathway is generally considered to be involved in maintaining the asymmetrical Gram-negative outer membrane via retrograde lipid transport. The pathway is composed of 3 components: the outer membrane MlaA-OmpC/F complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Here we provide evidence that the pathway may function in an anterograde direction by showing the inner membrane MlaFEDB machinery exports phospholipids from the inner membrane and transfers them to MlaC in the periplasm. This suggests for the first time that the Mla system may play a role in lipid export to the outer membrane rather than import as previous suggested. Interestingly, this lipid export process was shown to be independent of ATP. Furthermore, we confirm that the lipid transfer event occurs through the MlaD component of the MlaFEDB complex. We also solve the crystal structure of MlaC in its closed conformation, lacking bound lipid, revealing a novel pivoting β-sheet mechanism which functions to open and close the lipid-binding pocket.