1. Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system.
- Author
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Hughes GW, Hall SCL, Laxton CS, Sridhar P, Mahadi AH, Hatton C, Piggot TJ, Wotherspoon PJ, Leney AC, Ward DG, Jamshad M, Spana V, Cadby IT, Harding C, Isom GL, Bryant JA, Parr RJ, Yakub Y, Jeeves M, Huber D, Henderson IR, Clifton LA, Lovering AL, and Knowles TJ
- Subjects
- ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters metabolism, Bacterial Proteins chemistry, Bacterial Proteins genetics, Biological Transport, Crystallography, X-Ray, Gram-Negative Bacteria metabolism, Membrane Proteins genetics, Membrane Transport Proteins chemistry, Membrane Transport Proteins metabolism, Models, Biological, Multiprotein Complexes genetics, Multiprotein Complexes metabolism, Periplasm metabolism, Protein Binding, Protein Conformation, beta-Strand, Bacterial Proteins metabolism, Cell Membrane metabolism, Membrane Proteins metabolism, Phospholipids metabolism
- Abstract
The Mla pathway is believed to be involved in maintaining the asymmetrical Gram-negative outer membrane via retrograde phospholipid transport. The pathway is composed of three components: the outer membrane MlaA-OmpC/F complex, a soluble periplasmic protein, MlaC, and the inner membrane ATPase, MlaFEDB complex. Here, we solve the crystal structure of MlaC in its phospholipid-free closed apo conformation, revealing a pivoting β-sheet mechanism that functions to open and close the phospholipid-binding pocket. Using the apo form of MlaC, we provide evidence that the inner-membrane MlaFEDB machinery exports phospholipids to MlaC in the periplasm. Furthermore, we confirm that the phospholipid export process occurs through the MlaD component of the MlaFEDB complex and that this process is independent of ATP. Our data provide evidence of an apparatus for lipid export away from the inner membrane and suggest that the Mla pathway may have a role in anterograde phospholipid transport.
- Published
- 2019
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