Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA

Despite the importance of Mg2+ for numerous cellular activities, the mechanisms underlying its import and homeostasis are poorly understood. The CorA family is ubiquitous and is primarily responsible for Mg2+ transport. However, the key questions—such as, the ion selectivity, the transport pathway,...

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Main Authors: Nordin, N., Engman, H., Lundback, A.-K., Phua, T., Jong, Agnes Jin Oi, Cornvik, Tobias Carl, Guskov, Albert, Reynaud, Aline, Eshaghi, Said
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2013
Subjects:
Online Access:https://hdl.handle.net/10356/97900
http://hdl.handle.net/10220/12345
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author Nordin, N.
Engman, H.
Lundback, A.-K.
Phua, T.
Jong, Agnes Jin Oi
Cornvik, Tobias Carl
Guskov, Albert
Reynaud, Aline
Eshaghi, Said
author2 School of Biological Sciences
author_facet School of Biological Sciences
Nordin, N.
Engman, H.
Lundback, A.-K.
Phua, T.
Jong, Agnes Jin Oi
Cornvik, Tobias Carl
Guskov, Albert
Reynaud, Aline
Eshaghi, Said
author_sort Nordin, N.
collection NTU
description Despite the importance of Mg2+ for numerous cellular activities, the mechanisms underlying its import and homeostasis are poorly understood. The CorA family is ubiquitous and is primarily responsible for Mg2+ transport. However, the key questions—such as, the ion selectivity, the transport pathway, and the gating mechanism—have remained unanswered for this protein family. We present a 3.2 Å resolution structure of the archaeal CorA from Methanocaldococcus jannaschii, which is a unique complete structure of a CorA protein and reveals the organization of the selectivity filter, which is composed of the signature motif of this family. The structure reveals that polar residues facing the channel coordinate a partially hydrated Mg2+ during the transport. Based on these findings, we propose a unique gating mechanism involving a helical turn upon the binding of Mg2+ to the regulatory intracellular binding sites, and thus converting a polar ion passage into a narrow hydrophobic pore. Because the amino acids involved in the uptake, transport, and gating are all conserved within the entire CorA family, we believe this mechanism is general for the whole family including the eukaryotic homologs.
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spelling ntu-10356/979002023-02-28T16:55:49Z Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA Nordin, N. Engman, H. Lundback, A.-K. Phua, T. Jong, Agnes Jin Oi Cornvik, Tobias Carl Guskov, Albert Reynaud, Aline Eshaghi, Said School of Biological Sciences DRNTU::Science::Biological sciences Despite the importance of Mg2+ for numerous cellular activities, the mechanisms underlying its import and homeostasis are poorly understood. The CorA family is ubiquitous and is primarily responsible for Mg2+ transport. However, the key questions—such as, the ion selectivity, the transport pathway, and the gating mechanism—have remained unanswered for this protein family. We present a 3.2 Å resolution structure of the archaeal CorA from Methanocaldococcus jannaschii, which is a unique complete structure of a CorA protein and reveals the organization of the selectivity filter, which is composed of the signature motif of this family. The structure reveals that polar residues facing the channel coordinate a partially hydrated Mg2+ during the transport. Based on these findings, we propose a unique gating mechanism involving a helical turn upon the binding of Mg2+ to the regulatory intracellular binding sites, and thus converting a polar ion passage into a narrow hydrophobic pore. Because the amino acids involved in the uptake, transport, and gating are all conserved within the entire CorA family, we believe this mechanism is general for the whole family including the eukaryotic homologs. Published Version 2013-07-26T02:33:32Z 2019-12-06T19:48:00Z 2013-07-26T02:33:32Z 2019-12-06T19:48:00Z 2012 2012 Journal Article Guskov, A., Nordin, N., Reynaud, A., Engman, H., Lundback, A. K., Jong, A. J. O., et al. (2012). Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA. Proceedings of the national academy of sciences, 109(45), 18459-18464. https://hdl.handle.net/10356/97900 http://hdl.handle.net/10220/12345 10.1073/pnas.1210076109 23091000 en Proceedings of the national academy of sciences © 2012 National Academy of Sciences. This paper was published in Proceedings of the national academy of sciences and is made available as an electronic reprint (preprint) with permission of National Academy of Sciences. The paper can be found at the following official DOI: [http://dx.doi.org/10.1073/pnas.1210076109]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf
spellingShingle DRNTU::Science::Biological sciences
Nordin, N.
Engman, H.
Lundback, A.-K.
Phua, T.
Jong, Agnes Jin Oi
Cornvik, Tobias Carl
Guskov, Albert
Reynaud, Aline
Eshaghi, Said
Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title_full Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title_fullStr Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title_full_unstemmed Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title_short Structural insights into the mechanisms of Mg2+ uptake, transport, and gating by CorA
title_sort structural insights into the mechanisms of mg2 uptake transport and gating by cora
topic DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/97900
http://hdl.handle.net/10220/12345
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