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Structure of the hexameric fungal plasma membrane proton pump in its autoinhibited state.
<div class='caption-title'>The cryo-EM structure of monomeric and hexameric Pma1.</div>
<div class='caption-title'>Hexamer contacts and proton entry funnel.</div>
Heit S, Geurts MMG, Murphy BJ, Corey RA, Mills DJ, Kühlbrandt W, Bublitz M
OpenAccess logo Sci Adv 7 eabj5255 (2021)
Cited: 15 times
EuropePMC logo PMID: 34757782

Abstract

The fungal plasma membrane H+-ATPase Pma1 is a vital enzyme, generating a proton-motive force that drives the import of essential nutrients. Autoinhibited Pma1 hexamers in the plasma membrane of starving fungi are activated by glucose signaling and subsequent phosphorylation of the autoinhibitory domain. As related P-type adenosine triphosphatases (ATPases) are not known to oligomerize, the physiological relevance of Pma1 hexamers remained unknown. We have determined the structure of hexameric Pma1 from Neurospora crassa by electron cryo-microscopy at 3.3-Å resolution, elucidating the molecular basis for hexamer formation and autoinhibition and providing a basis for structure-based drug development. Coarse-grained molecular dynamics simulations in a lipid bilayer suggest lipid-mediated contacts between monomers and a substantial protein-induced membrane deformation that could act as a proton-attracting funnel.

Articles - 7nxf mentioned but not cited (1)

  1. Structure of the hexameric fungal plasma membrane proton pump in its autoinhibited state. Heit S, Geurts MMG, Murphy BJ, Corey RA, Mills DJ, Kühlbrandt W, Bublitz M. Sci Adv 7 eabj5255 (2021)


Reviews citing this publication (4)

  1. Proton and calcium pumping P-type ATPases and their regulation of plant responses to the environment. Fuglsang AT, Palmgren M. Plant Physiol 187 1856-1875 (2021)
  2. P-type ATPases: Many more enigmas left to solve. Palmgren M. J Biol Chem 299 105352 (2023)
  3. Structural and Functional Diversity of Two ATP-Driven Plant Proton Pumps. Kabała K, Janicka M. Int J Mol Sci 24 4512 (2023)
  4. Fungal Plasma Membrane H+-ATPase: Structure, Mechanism, and Drug Discovery. Zhao CR, You ZL, Bai L. J Fungi (Basel) 10 273 (2024)

Articles citing this publication (10)

  1. Structure and activation mechanism of the hexameric plasma membrane H+-ATPase. Zhao P, Zhao C, Chen D, Yun C, Li H, Bai L. Nat Commun 12 6439 (2021)
  2. Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins. Jiménez-Ortigosa C, Jiang J, Chen M, Kuang X, Healey KR, Castellano P, Boparai N, Ludtke SJ, Perlin DS, Dai W. J Fungi (Basel) 7 120 (2021)
  3. The evolution of plant proton pump regulation via the R domain may have facilitated plant terrestrialization. Stéger A, Hayashi M, Lauritzen EW, Herburger K, Shabala L, Wang C, Bendtsen AK, Nørrevang AF, Madriz-Ordeñana K, Ren S, Trinh MDL, Thordal-Christensen H, Fuglsang AT, Shabala S, Østerberg JT, Palmgren M. Commun Biol 5 1312 (2022)
  4. Anionic Phospholipids Stimulate the Proton Pumping Activity of the Plant Plasma Membrane P-Type H+-ATPase. Paweletz LC, Holtbrügge SL, Löb M, De Vecchis D, Schäfer LV, Günther Pomorski T, Justesen BH. Int J Mol Sci 24 13106 (2023)
  5. Phosphoregulation of the yeast Pma1 H+-ATPase autoinhibitory domain involves the Ptk1/2 kinases and the Glc7 PP1 phosphatase and is under TORC1 control. Guarini N, Saliba E, André B. PLoS Genet 20 e1011121 (2024)
  6. Plasma membrane H+-ATPases promote TORC1 activation in plant suspension cells. Primo C, Navarre C, Chaumont F, André B. iScience 25 104238 (2022)
  7. Published Erratum Correction: Jiménez-Ortigosa et al. Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins. J. Fungi 2021, 7, 120. Jiménez-Ortigosa C, Jiang J, Chen M, Kuang X, Healey KR, Castellano P, Boparai N, Ludtke SJ, Perlin DS, Dai W. J Fungi (Basel) 10 201 (2024)
  8. ERMA (TMEM94) is a P-type ATPase transporter for Mg2+ uptake in the endoplasmic reticulum. Vishnu N, Venkatesan M, Madaris TR, Venkateswaran MK, Stanley K, Ramachandran K, Chidambaram A, Madesh AK, Yang W, Nair J, Narkunan M, Muthukumar T, Karanam V, Joseph LC, Le A, Osidele A, Aslam MI, Morrow JP, Malicdan MC, Stathopulos PB, Madesh M. Mol Cell 84 1321-1337.e11 (2024)
  9. Light-induced stomatal opening requires phosphorylation of the C-terminal autoinhibitory domain of plasma membrane H+-ATPase. Fuji S, Yamauchi S, Sugiyama N, Kohchi T, Nishihama R, Shimazaki KI, Takemiya A. Nat Commun 15 1195 (2024)
  10. Uncovering diffusive states of the yeast membrane protein, Pma1, and how labeling method can change diffusive behavior. Bailey MLP, Pratt SE, Hinrichsen M, Zhang Y, Bewersdorf J, Regan LJ, Mochrie SGJ. Eur Phys J E Soft Matter 46 42 (2023)


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