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Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters

Landreh, M.; Marklund, E.G.; Uzdavinys, P.; Degiacomi, M.T.; Coincon, M.; Gault, J.; Gupta, K.; Liko, I.; Benesch, J.L.P.; Drew, D.; Robinson, C.V.

Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters Thumbnail


Authors

M. Landreh

E.G. Marklund

P. Uzdavinys

M. Coincon

J. Gault

K. Gupta

I. Liko

J.L.P. Benesch

D. Drew

C.V. Robinson



Abstract

Na+/H+ antiporters are found in all kingdoms of life and exhibit catalysis rates that are among the fastest of all known secondary-active transporters. Here we combine ion mobility mass spectrometry and molecular dynamics simulations to study the conformational stability and lipid-binding properties of the Na+/H+ exchanger NapA from Thermus thermophilus and compare this to the prototypical antiporter NhaA from Escherichia coli and the human homologue NHA2. We find that NapA and NHA2, but not NhaA, form stable dimers and do not selectively retain membrane lipids. By comparing wild-type NapA with engineered variants, we show that the unfolding of the protein in the gas phase involves the disruption of inter-domain contacts. Lipids around the domain interface protect the native fold in the gas phase by mediating contacts between the mobile protein segments. We speculate that elevator-type antiporters such as NapA, and likely NHA2, use a subset of annular lipids as structural support to facilitate large-scale conformational changes within the membrane.

Citation

Landreh, M., Marklund, E., Uzdavinys, P., Degiacomi, M., Coincon, M., Gault, J., …Robinson, C. (2017). Integrating mass spectrometry with MD simulations reveals the role of lipids in Na+/H+ antiporters. Nature Communications, 8, Article 13993. https://doi.org/10.1038/ncomms13993

Journal Article Type Article
Acceptance Date Nov 18, 2016
Online Publication Date Jan 10, 2017
Publication Date Jan 10, 2017
Deposit Date Jul 26, 2017
Publicly Available Date Mar 29, 2024
Journal Nature Communications
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 8
Article Number 13993
DOI https://doi.org/10.1038/ncomms13993

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