Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA

Hendrik R Sikkema; Marco van den Noort; Jan Rheinberger; Marijn de Boer; Sabrina T Krepel; Gea K Schuurman-Wolters; Cristina Paulino; Bert Poolman

doi:10.1126/sciadv.abd7697

Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA

Hendrik R Sikkema, Marco van den Noort, Jan Rheinberger, Marijn de Boer, Sabrina T Krepel, Gea K Schuurman-Wolters, Cristina Paulino^*, Bert Poolman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

27 Downloads (Pure)

Abstract

(Micro)organisms are exposed to fluctuating environmental conditions, and adaptation to stress is essential for survival. Increased osmolality (hypertonicity) causes outflow of water and loss of turgor and is dangerous if the cell is not capable of rapidly restoring its volume. The osmoregulatory adenosine triphosphate-binding cassette transporter OpuA restores the cell volume by accumulating large amounts of compatible solute. OpuA is gated by ionic strength and inhibited by the second messenger cyclic-di-AMP, a molecule recently shown to affect many cellular processes. Despite the master regulatory role of cyclic-di-AMP, structural and functional insights into how the second messenger regulates (transport) proteins on the molecular level are lacking. Here, we present high-resolution cryo-electron microscopy structures of OpuA and in vitro activity assays that show how the osmoregulator OpuA is activated by high ionic strength and how cyclic-di-AMP acts as a backstop to prevent unbridled uptake of compatible solutes.

Original language	English
Article number	eabd7697
Number of pages	12
Journal	Science Advances
Volume	6
Issue number	47
DOIs	https://doi.org/10.1126/sciadv.abd7697
Publication status	Published - Nov-2020

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Gating by ionic strength andsafety check by cyclic-di-AMP intheABC transporter OpuAFinal publisher's version, 1.08 MBLicence: CC BY-NC

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@article{e8ad211044c548b8aff55bb2f05cdf6e,

title = "Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA",

abstract = "(Micro)organisms are exposed to fluctuating environmental conditions, and adaptation to stress is essential for survival. Increased osmolality (hypertonicity) causes outflow of water and loss of turgor and is dangerous if the cell is not capable of rapidly restoring its volume. The osmoregulatory adenosine triphosphate-binding cassette transporter OpuA restores the cell volume by accumulating large amounts of compatible solute. OpuA is gated by ionic strength and inhibited by the second messenger cyclic-di-AMP, a molecule recently shown to affect many cellular processes. Despite the master regulatory role of cyclic-di-AMP, structural and functional insights into how the second messenger regulates (transport) proteins on the molecular level are lacking. Here, we present high-resolution cryo-electron microscopy structures of OpuA and in vitro activity assays that show how the osmoregulator OpuA is activated by high ionic strength and how cyclic-di-AMP acts as a backstop to prevent unbridled uptake of compatible solutes.",

author = "Sikkema, {Hendrik R} and {van den Noort}, Marco and Jan Rheinberger and {de Boer}, Marijn and Krepel, {Sabrina T} and Schuurman-Wolters, {Gea K} and Cristina Paulino and Bert Poolman",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",

year = "2020",

month = nov,

doi = "10.1126/sciadv.abd7697",

language = "English",

volume = "6",

journal = "Science Advances",

issn = "2375-2548",

publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

number = "47",

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Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA. / Sikkema, Hendrik R; van den Noort, Marco; Rheinberger, Jan; de Boer, Marijn; Krepel, Sabrina T; Schuurman-Wolters, Gea K; Paulino, Cristina ; Poolman, Bert.

In: Science Advances, Vol. 6, No. 47, eabd7697, 11.2020.

Research output: Contribution to journal › Article › Academic › peer-review

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T1 - Gating by ionic strength and safety check by cyclic-di-AMP in the ABC transporter OpuA

AU - Sikkema, Hendrik R

AU - van den Noort, Marco

AU - Rheinberger, Jan

AU - de Boer, Marijn

AU - Krepel, Sabrina T

AU - Schuurman-Wolters, Gea K

AU - Paulino, Cristina

AU - Poolman, Bert

N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2020/11

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N2 - (Micro)organisms are exposed to fluctuating environmental conditions, and adaptation to stress is essential for survival. Increased osmolality (hypertonicity) causes outflow of water and loss of turgor and is dangerous if the cell is not capable of rapidly restoring its volume. The osmoregulatory adenosine triphosphate-binding cassette transporter OpuA restores the cell volume by accumulating large amounts of compatible solute. OpuA is gated by ionic strength and inhibited by the second messenger cyclic-di-AMP, a molecule recently shown to affect many cellular processes. Despite the master regulatory role of cyclic-di-AMP, structural and functional insights into how the second messenger regulates (transport) proteins on the molecular level are lacking. Here, we present high-resolution cryo-electron microscopy structures of OpuA and in vitro activity assays that show how the osmoregulator OpuA is activated by high ionic strength and how cyclic-di-AMP acts as a backstop to prevent unbridled uptake of compatible solutes.

AB - (Micro)organisms are exposed to fluctuating environmental conditions, and adaptation to stress is essential for survival. Increased osmolality (hypertonicity) causes outflow of water and loss of turgor and is dangerous if the cell is not capable of rapidly restoring its volume. The osmoregulatory adenosine triphosphate-binding cassette transporter OpuA restores the cell volume by accumulating large amounts of compatible solute. OpuA is gated by ionic strength and inhibited by the second messenger cyclic-di-AMP, a molecule recently shown to affect many cellular processes. Despite the master regulatory role of cyclic-di-AMP, structural and functional insights into how the second messenger regulates (transport) proteins on the molecular level are lacking. Here, we present high-resolution cryo-electron microscopy structures of OpuA and in vitro activity assays that show how the osmoregulator OpuA is activated by high ionic strength and how cyclic-di-AMP acts as a backstop to prevent unbridled uptake of compatible solutes.

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