IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38944-1.html
   My bibliography  Save this article

Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation

Author

Listed:
  • Michael F. Fuss

    (Goethe University Frankfurt)

  • Jan-Philip Wieferig

    (Max Planck Institute of Biophysics)

  • Robin A. Corey

    (University of Oxford
    University of Bristol)

  • Yvonne Hellmich

    (Goethe University Frankfurt)

  • Igor Tascón

    (Goethe University Frankfurt
    University of the Basque Country
    Ikerbasque, Basque Foundation for Science)

  • Joana S. Sousa

    (Max Planck Institute of Biophysics
    UCB Pharma, UCB Biopharma UK)

  • Phillip J. Stansfeld

    (University of Warwick)

  • Janet Vonck

    (Max Planck Institute of Biophysics)

  • Inga Hänelt

    (Goethe University Frankfurt)

Abstract

Cyclic di-AMP is the only known essential second messenger in bacteria and archaea, regulating different proteins indispensable for numerous physiological processes. In particular, it controls various potassium and osmolyte transporters involved in osmoregulation. In Bacillus subtilis, the K+/H+ symporter KimA of the KUP family is inactivated by c-di-AMP. KimA sustains survival at potassium limitation at low external pH by mediating potassium ion uptake. However, at elevated intracellular K+ concentrations, further K+ accumulation would be toxic. In this study, we reveal the molecular basis of how c-di-AMP binding inhibits KimA. We report cryo-EM structures of KimA with bound c-di-AMP in detergent solution and reconstituted in amphipols. By combining structural data with functional assays and molecular dynamics simulations we reveal how c-di-AMP modulates transport. We show that an intracellular loop in the transmembrane domain interacts with c-di-AMP bound to the adjacent cytosolic domain. This reduces the mobility of transmembrane helices at the cytosolic side of the K+ binding site and therefore traps KimA in an inward-occluded conformation.

Suggested Citation

  • Michael F. Fuss & Jan-Philip Wieferig & Robin A. Corey & Yvonne Hellmich & Igor Tascón & Joana S. Sousa & Phillip J. Stansfeld & Janet Vonck & Inga Hänelt, 2023. "Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38944-1
    DOI: 10.1038/s41467-023-38944-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38944-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-38944-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexey Rozov & Iskander Khusainov & Kamel El Omari & Ramona Duman & Vitaliy Mykhaylyk & Marat Yusupov & Eric Westhof & Armin Wagner & Gulnara Yusupova, 2019. "Importance of potassium ions for ribosome structure and function revealed by long-wavelength X-ray diffraction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Arthur Prindle & Jintao Liu & Munehiro Asally & San Ly & Jordi Garcia-Ojalvo & Gürol M. Süel, 2015. "Ion channels enable electrical communication in bacterial communities," Nature, Nature, vol. 527(7576), pages 59-63, November.
    3. Ekaitz Errasti-Murugarren & Joana Fort & Paola Bartoccioni & Lucía Díaz & Els Pardon & Xavier Carpena & Meritxell Espino-Guarch & Antonio Zorzano & Christine Ziegler & Jan Steyaert & Juan Fernández-Re, 2019. "L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jakob M. Silberberg & Sophie Ketter & Paul J. N. Böhm & Kristin Jordan & Marcel Wittenberg & Julia Grass & Inga Hänelt, 2024. "KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuhan Zhang & Yongbin Wang & Zhibin Chen & Chengzhi Hu & Jiuhui Qu, 2024. "Recovering nutrients and unblocking the cake layer of an electrochemical anaerobic membrane bioreactor," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Ashty S. Karim & Dylan M. Brown & Chloé M. Archuleta & Sharisse Grannan & Ludmilla Aristilde & Yogesh Goyal & Josh N. Leonard & Niall M. Mangan & Arthur Prindle & Gabriel J. Rocklin & Keith J. Tyo & L, 2024. "Deconstructing synthetic biology across scales: a conceptual approach for training synthetic biologists," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Vivek Singh & Yuzuru Itoh & Samuel Del’Olio & Asem Hassan & Andreas Naschberger & Rasmus Kock Flygaard & Yuko Nobe & Keiichi Izumikawa & Shintaro Aibara & Juni Andréll & Paul C. Whitford & Antoni Barr, 2024. "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    5. K. Shanmugha Rajan & Hava Madmoni & Anat Bashan & Masato Taoka & Saurav Aryal & Yuko Nobe & Tirza Doniger & Beathrice Galili Kostin & Amit Blumberg & Smadar Cohen-Chalamish & Schraga Schwartz & Andre , 2023. "A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Josep Rullo-Tubau & Maria Martinez-Molledo & Paola Bartoccioni & Ignasi Puch-Giner & Ángela Arias & Suwipa Saen-Oon & Camille Stephan-Otto Attolini & Rafael Artuch & Lucía Díaz & Víctor Guallar & Ekai, 2024. "Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Martin F. Peter & Jan A. Ruland & Peer Depping & Niels Schneberger & Emmanuele Severi & Jonas Moecking & Karl Gatterdam & Sarah Tindall & Alexandre Durand & Veronika Heinz & Jan Peter Siebrasse & Paul, 2022. "Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Yan, Xuejun & Lee, Hyung-Sool & Li, Nan & Wang, Xin, 2020. "The micro-niche of exoelectrogens influences bioelectricity generation in bioelectrochemical systems," Renewable and Sustainable Energy Reviews, Elsevier, vol. 134(C).
    9. Joanne L. Parker & Justin C. Deme & Dimitrios Kolokouris & Gabriel Kuteyi & Philip C. Biggin & Susan M. Lea & Simon Newstead, 2021. "Molecular basis for redox control by the human cystine/glutamate antiporter system xc−," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    10. Christwardana, Marcelinus & Frattini, Domenico & Accardo, Grazia & Yoon, Sung Pil & Kwon, Yongchai, 2018. "Early-stage performance evaluation of flowing microbial fuel cells using chemically treated carbon felt and yeast biocatalyst," Applied Energy, Elsevier, vol. 222(C), pages 369-382.
    11. Jana Aupič & Jure Borišek & Sebastian M. Fica & Wojciech P. Galej & Alessandra Magistrato, 2023. "Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    12. Simon A. Fromm & Kate M. O’Connor & Michael Purdy & Pramod R. Bhatt & Gary Loughran & John F. Atkins & Ahmad Jomaa & Simone Mattei, 2023. "The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    13. Na Chen & Na Du & Ruichen Shen & Tianpei He & Jing Xi & Jie Tan & Guangkai Bian & Yanbing Yang & Tiangang Liu & Weihong Tan & Lilei Yu & Quan Yuan, 2023. "Redox signaling-driven modulation of microbial biosynthesis and biocatalysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    14. Yongchan Lee & Pattama Wiriyasermkul & Pornparn Kongpracha & Satomi Moriyama & Deryck J. Mills & Werner Kühlbrandt & Shushi Nagamori, 2022. "Ca2+-mediated higher-order assembly of heterodimers in amino acid transport system b0,+ biogenesis and cystinuria," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Xiaoling Zhai & Joseph W Larkin & Kaito Kikuchi & Samuel E Redford & Ushasi Roy & Gürol M Süel & Andrew Mugler, 2019. "Statistics of correlated percolation in a bacterial community," PLOS Computational Biology, Public Library of Science, vol. 15(12), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38944-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.