M. Landreh
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.
Authors
E.G. Marklund
P. Uzdavinys
Matteo Degiacomi matteo.t.degiacomi@durham.ac.uk
Part Time Teacher
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 | Aug 2, 2017 |
Journal | Nature Communications |
Publisher | Nature Research |
Peer Reviewed | Peer Reviewed |
Volume | 8 |
Article Number | 13993 |
DOI | https://doi.org/10.1038/ncomms13993 |
Public URL | https://durham-repository.worktribe.com/output/1372654 |
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