Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system

Gareth Hughes; Stephen Hall; Claire Laxton; Pooja Sridhar; Amirul Mahadi; Caitlin Hatton; Thomas Piggot; Peter Wotherspoon; Aneika Leney; Douglas Ward; Mohammed Jamshad; Vaclav Spana; Ian Cadby; Christopher Harding; Georgia Isom; Jack Bryant; Rebecca Parr; Yasin Yakub; Mark Jeeves; Damon Huber; Ian Henderson; Luke Clifton; Andrew Lovering; Timothy Knowles

doi:10.1038/s41564-019-0481-y

Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system

Gareth Hughes, Stephen Hall, Claire Laxton, Pooja Sridhar, Amirul Mahadi, Caitlin Hatton, Thomas Piggot, Peter Wotherspoon, Aneika Leney, Douglas Ward, Mohammed Jamshad, Vaclav Spana, Ian Cadby, Christopher Harding, Georgia Isom, Jack Bryant, Rebecca Parr, Yasin Yakub, Mark Jeeves, Damon HuberIan Henderson, Luke Clifton, Andrew Lovering, Timothy Knowles

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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 3 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 which 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 provides evidence of an apparatus for lipid export away from the inner membrane and suggests that the Mla pathway may have a role in anterograde phospholipid transport.

Original language	English
Pages (from-to)	1692–1705
Number of pages	14
Journal	Nature Microbiology
Volume	4
Issue number	10
Early online date	24 Jun 2019
DOIs	https://doi.org/10.1038/s41564-019-0481-y
Publication status	Published - Oct 2019

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Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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Hughes_et_al_Evidence_for_phospholipid_export_from_the_bacterial_inner_membrane_by_the_Mla_ABC_transport_system_Nature_Microbiology_2019
This is the accepted manuscript for a publication in Nature Microbiology, the final published version is available at: https://doi.org/10.1038/s41564-019-0481-y
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Hughes, G., Hall, S., Laxton, C., Sridhar, P., Mahadi, A., Hatton, C., Piggot, T., Wotherspoon, P., Leney, A., Ward, D., Jamshad, M., Spana, V., Cadby, I., Harding, C., Isom, G., Bryant, J., Parr, R., Yakub, Y., Jeeves, M., ... Knowles, T. (2019). Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system. Nature Microbiology, 4(10), 1692–1705. https://doi.org/10.1038/s41564-019-0481-y

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title = "Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system",

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 3 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 which 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 provides evidence of an apparatus for lipid export away from the inner membrane and suggests that the Mla pathway may have a role in anterograde phospholipid transport. ",

author = "Gareth Hughes and Stephen Hall and Claire Laxton and Pooja Sridhar and Amirul Mahadi and Caitlin Hatton and Thomas Piggot and Peter Wotherspoon and Aneika Leney and Douglas Ward and Mohammed Jamshad and Vaclav Spana and Ian Cadby and Christopher Harding and Georgia Isom and Jack Bryant and Rebecca Parr and Yasin Yakub and Mark Jeeves and Damon Huber and Ian Henderson and Luke Clifton and Andrew Lovering and Timothy Knowles",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2019",

month = oct,

doi = "10.1038/s41564-019-0481-y",

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Hughes, G, Hall, S, Laxton, C, Sridhar, P, Mahadi, A, Hatton, C, Piggot, T, Wotherspoon, P, Leney, A , Ward, D , Jamshad, M, Spana, V, Cadby, I, Harding, C, Isom, G, Bryant, J, Parr, R, Yakub, Y, Jeeves, M , Huber, D, Henderson, I, Clifton, L, Lovering, A & Knowles, T 2019, 'Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system', Nature Microbiology, vol. 4, no. 10, pp. 1692–1705. https://doi.org/10.1038/s41564-019-0481-y

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AU - Hatton, Caitlin

AU - Piggot, Thomas

AU - Wotherspoon, Peter

AU - Leney, Aneika

AU - Ward, Douglas

AU - Jamshad, Mohammed

AU - Spana, Vaclav

AU - Cadby, Ian

AU - Harding, Christopher

AU - Isom, Georgia

AU - Bryant, Jack

AU - Parr, Rebecca

AU - Yakub, Yasin

AU - Jeeves, Mark

AU - Huber, Damon

AU - Henderson, Ian

AU - Clifton, Luke

AU - Lovering, Andrew

AU - Knowles, Timothy

PY - 2019/10

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N2 - 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 3 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 which 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 provides evidence of an apparatus for lipid export away from the inner membrane and suggests that the Mla pathway may have a role in anterograde phospholipid transport.

AB - 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 3 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 which 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 provides evidence of an apparatus for lipid export away from the inner membrane and suggests that the Mla pathway may have a role in anterograde phospholipid transport.

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EP - 1705

JO - Nature Microbiology

JF - Nature Microbiology

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Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system

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