Luan, S. & Wang, C. Calcium signaling mechanisms across kingdoms. Annu. Rev. Cell Dev. Biol. 37, 311–340 (2021).
CAS
PubMed
Google Scholar
Stock, C. et al. Fast-forward on P-type ATPases: recent advances on structure and function. Biochem. Soc. Trans. 51, 1347–1360 (2023).
CAS
PubMed
Google Scholar
Vulpe, C., Levinson, B., Whitney, S., Packman, S. & Gitschier, J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat. Genet. 3, 7–13 (1993).
CAS
PubMed
Google Scholar
Jacobsen, N. J. et al. ATP2A2 mutations in Darier’s disease and their relationship to neuropsychiatric phenotypes. Hum. Mol. Genet. 8, 1631–1636 (1999).
CAS
PubMed
Google Scholar
Odermatt, A. et al. The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease. Hum. Genet. 106, 482–491 (2000).
CAS
PubMed
Google Scholar
Sudbrak, R. et al. Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca2+ pump. Hum. Mol. Genet. 9, 1131–1140 (2000).
CAS
PubMed
Google Scholar
De Fusco, M. et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat. Genet. 33, 192–196 (2003).
PubMed
Google Scholar
de Carvalho Aguiar, P. et al. Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 43, 169–175 (2004).
PubMed
Google Scholar
Brini, M. et al. Plasma-membrane calcium pumps and hereditary deafness. Biochem. Soc. Trans. 35, 913–918 (2007).
CAS
PubMed
Google Scholar
Schwinger, R. H., Bundgaard, H., Muller-Ehmsen, J. & Kjeldsen, K. The Na, K-ATPase in the failing human heart. Cardiovasc. Res. 57, 913–920 (2003).
CAS
PubMed
Google Scholar
Schubert, M. L. & Peura, D. A. Control of gastric acid secretion in health and disease. Gastroenterology 134, 1842–1860 (2008).
CAS
PubMed
Google Scholar
Dyla, M., Basse Hansen, S., Nissen, P. & Kjaergaard, M. Structural dynamics of P-type ATPase ion pumps. Biochem. Soc. Trans. 47, 1247–1257 (2019).
CAS
PubMed
Google Scholar
Albers, R. W. Biochemical aspects of active transport. Annu. Rev. Biochem. 36, 727–756 (1967).
CAS
PubMed
Google Scholar
Moller, J. V., Olesen, C., Winther, A. M. & Nissen, P. The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump. Q. Rev. Biophys. 43, 501–566 (2010).
PubMed
Google Scholar
Wu, M. et al. Structure and transport mechanism of the human calcium pump SPCA1. Cell Res. 33, 533–545 (2023).
CAS
PubMed
PubMed Central
Google Scholar
Gong, D. et al. Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin. Nat. Commun. 9, 3623 (2018).
ADS
PubMed
PubMed Central
Google Scholar
Berridge, M. J., Lipp, P. & Bootman, M. D. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1, 11–21 (2000).
CAS
PubMed
Google Scholar
Constantin, C. E. et al. Ca2+-pumping by PMCA-Neuroplastin complexes operates in the kiloHertz-range. Nat. Commun. https://doi.org/10.1038/s41467-025-62735-5 (2025).
Schmidt, N. et al. Neuroplastin and basigin are essential auxiliary subunits of plasma membrane Ca2+-ATPases and key regulators of Ca2+ clearance. Neuron 96, 827–838.e9 (2017).
CAS
PubMed
Google Scholar
Niggli, V., Adunyah, E. S. & Carafoli, E. Acidic phospholipids, unsaturated fatty acids, and limited proteolysis mimic the effect of calmodulin on the purified erythrocyte Ca2+-ATPase. J. Biol. Chem. 256, 8588–8592 (1981).
CAS
PubMed
Google Scholar
Missiaen, L., Wuytack, F., Raeymaekers, L., De Smedt, H. & Casteels, R. Polyamines and neomycin inhibit the purified plasma-membrane Ca2+ pump by interacting with associated polyphosphoinositides. Biochem. J. 261, 1055–1058 (1989).
CAS
PubMed
PubMed Central
Google Scholar
Peinelt, C. & Apell, H. J. Time-resolved charge movements in the sarcoplasmatic reticulum Ca-ATPase. Biophys. J. 86, 815–824 (2004).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Dode, L. et al. Dissection of the functional differences between human secretory pathway Ca2+/Mn2+-ATPase (SPCA) 1 and 2 isoenzymes by steady-state and transient kinetic analyses. J. Biol. Chem. 281, 3182–3189 (2006).
CAS
PubMed
Google Scholar
Liang, M. et al. Identification of a pool of non-pumping Na/K-ATPase. J. Biol. Chem. 282, 10585–10593 (2007).
CAS
PubMed
Google Scholar
Schultz, J. M. et al. Modification of human hearing loss by plasma-membrane calcium pump PMCA2. N. Engl. J. Med. 352, 1557–1564 (2005).
CAS
PubMed
Google Scholar
Ficarella, R. et al. A functional study of plasma-membrane calcium-pump isoform 2 mutants causing digenic deafness. Proc. Natl Acad. Sci. USA 104, 1516–1521 (2007).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Kabashima, Y., Ogawa, H., Nakajima, R. & Toyoshima, C. What ATP binding does to the Ca2+ pump and how nonproductive phosphoryl transfer is prevented in the absence of Ca2. Proc. Natl Acad. Sci. USA 117, 18448–18458 (2020).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Mintz, E., Mata, A. M., Forge, V., Passafiume, M. & Guillain, F. The modulation of Ca2+ binding to sarcoplasmic reticulum ATPase by ATP analogues is pH-dependent. J. Biol. Chem. 270, 27160–27164 (1995).
CAS
PubMed
Google Scholar
Winther, A. M. et al. The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm. Nature 495, 265–269 (2013).
ADS
CAS
PubMed
Google Scholar
Beesley, P. W., Herrera-Molina, R., Smalla, K. H. & Seidenbecher, C. The neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function. J. Neurochem. 131, 268–283 (2014).
CAS
PubMed
Google Scholar
Rathod, N. et al. Nothing regular about the regulins: distinct functional properties of SERCA transmembrane peptide regulatory subunits. Int. J. Mol. Sci. 22, 8891 (2021).
Boudkkazi, S. et al. A noelin-organized extracellular network of proteins required for constitutive and context-dependent anchoring of AMPA-receptors. Neuron 111, 2544–2556.e9 (2023).
CAS
PubMed
PubMed Central
Google Scholar
Chen, Z. et al. Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. Sci. Adv. 9, eadd9742 (2023).
CAS
PubMed
PubMed Central
Google Scholar
Hansen, S. B. et al. The crystal structure of the Ca2+-ATPase 1 from Listeria monocytogenes reveals a pump primed for dephosphorylation. J. Mol. Biol. 433, 167015 (2021).
CAS
PubMed
Google Scholar
Zhang, Y. et al. Multiple sub-state structures of SERCA2b reveal conformational overlap at transition steps during the catalytic cycle. Cell Rep. 41, 111760 (2022).
CAS
PubMed
Google Scholar
Roderer, D., Schubert, E., Sitsel, O. & Raunser, S. Towards the application of Tc toxins as a universal protein translocation system. Nat. Commun. 10, 5263 (2019).
ADS
PubMed
PubMed Central
Google Scholar
Toyoshima, C., Nakasako, M., Nomura, H. & Ogawa, H. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405, 647–655 (2000).
ADS
CAS
PubMed
Google Scholar
Inesi, G., Kurzmack, M., Coan, C. & Lewis, D. E. Cooperative calcium binding and ATPase activation in sarcoplasmic reticulum vesicles. J. Biol. Chem. 255, 3025–3031 (1980).
CAS
PubMed
Google Scholar
Takahashi, K. & Kitamura, K. A point mutation in a plasma membrane Ca2+-ATPase gene causes deafness in Wriggle mouse Sagami. Biochem. Biophys. Res. Commun. 261, 773–778 (1999).
CAS
PubMed
Google Scholar
Toyoshima, C. et al. Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state. Nature 495, 260–264 (2013).
ADS
CAS
PubMed
Google Scholar
Espinoza-Fonseca, L. M. The Ca2+-ATPase pump facilitates bidirectional proton transport across the sarco/endoplasmic reticulum. Mol. Biosyst. 13, 633–637 (2017).
CAS
PubMed
PubMed Central
Google Scholar
Bublitz, M. et al. Ion pathways in the sarcoplasmic reticulum Ca2+-ATPase. J. Biol. Chem. 288, 10759–10765 (2013).
CAS
PubMed
PubMed Central
Google Scholar
Ahmad, S. et al. Structural basis for effector transmembrane domain recognition by type VI secretion system chaperones. eLife 9, e62816 (2020).
CAS
PubMed
PubMed Central
Google Scholar
Spiden, S. L. et al. The novel mouse mutation Oblivion inactivates the PMCA2 pump and causes progressive hearing loss. PLoS Genet. 4, e1000238 (2008).
PubMed
PubMed Central
Google Scholar
Rahimi, M. J. et al. De novo variants in ATP2B1 lead to neurodevelopmental delay. Am. J. Hum. Genet. 109, 944–952 (2022).
CAS
PubMed
PubMed Central
Google Scholar
Choquette, D. et al. Regulation of plasma membrane Ca2+ ATPases by lipids of the phosphatidylinositol cycle. Biochem. Biophys. Res. Commun. 125, 908–915 (1984).
CAS
PubMed
Google Scholar
Iwasaki, H. et al. A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate. Proc. Natl Acad. Sci. USA 105, 7970–7975 (2008).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Sehgal, P. et al. Inhibition of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase by thapsigargin analogs induces cell death via ER Ca2+ depletion and the unfolded protein response. J. Biol. Chem. 292, 19656–19673 (2017).
CAS
PubMed
PubMed Central
Google Scholar
Espinoza-Fonseca, L. M., Autry, J. M., Ramirez-Salinas, G. L. & Thomas, D. D. Atomic-level mechanisms for phospholamban regulation of the calcium pump. Biophys. J. 108, 1697–1708 (2015).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Driggers, C. M., Kuo, Y. Y., Zhu, P., ElSheikh, A. & Shyng, S. L. Structure of an open KATP channel reveals tandem PIP2 binding sites mediating the Kir6.2 and SUR1 regulatory interface. Nat. Commun. 15, 2502 (2024).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Gao, S., Yao, X. & Yan, N. Structure of human Cav2.2 channel blocked by the painkiller ziconotide. Nature 596, 143–147 (2021).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Hansen, S. B., Tao, X. & MacKinnon, R. Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2. Nature 477, 495–498 (2011).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Lu, Y. et al. Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP2. Nat. Commun. 14, 6157 (2023).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Sun, J. & MacKinnon, R. Structural basis of human KCNQ1 modulation and gating. Cell 180, 340–347.e9 (2020).
CAS
PubMed
Google Scholar
Yin, Y. et al. Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP2. Science 378, eadd1268 (2022).
CAS
PubMed
PubMed Central
Google Scholar
Zhang, W. et al. Structural and functional insights into the lipid regulation of human anion exchanger 2. Nat. Commun. 15, 759 (2024).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Lindner, P., Christensen, S. B., Nissen, P., Moller, J. V. & Engedal, N. Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components. Cell Commun. Signal. 18, 12 (2020).
CAS
PubMed
PubMed Central
Google Scholar
Denmeade, S. R. et al. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer. J. Natl Cancer Inst. 95, 990–1000 (2003).
CAS
PubMed
Google Scholar
Denmeade, S. R. et al. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy. Sci. Transl. Med. 4, 140ra186 (2012).
Google Scholar
Quynh Doan, N. T. & Christensen, S. B. Thapsigargin, origin, chemistry, structure–activity relationships and prodrug development. Curr. Pharm. Des. 21, 5501–5517 (2015).
CAS
PubMed
Google Scholar
Murata, Y., Iwasaki, H., Sasaki, M., Inaba, K. & Okamura, Y. Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature 435, 1239–1243 (2005).
ADS
CAS
PubMed
Google Scholar
Tabata, S. et al. Electron microscopic detection of single membrane proteins by a specific chemical labeling. iScience 22, 256–268 (2019).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Lee, L. F. R. & Dall, P. M. Concurrent agreement between ActiGraph® and activPAL® in measuring moderate to vigorous intensity physical activity for adults. Med. Eng. Phys. 74, 82–88 (2019).
PubMed
Google Scholar
Drake, J. C., Allegra, C. J., Curt, G. A. & Chabner, B. A. Competitive protein-binding assay for trimetrexate. Cancer Treat. Rep. 69, 641–644 (1985).
CAS
PubMed
Google Scholar
Schulte, U. et al. Mitochondrial complexome reveals quality-control pathways of protein import. Nature 614, 153–159 (2023).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Kabsch, W. Xds. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).
ADS
CAS
PubMed
PubMed Central
Google Scholar
McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Stabrin, M. et al. TranSPHIRE: automated and feedback-optimized on-the-fly processing for cryo-EM. Nat. Commun. 11, 5716 (2020).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
CAS
PubMed
PubMed Central
Google Scholar
Rohou, A. & Grigorieff, N. CTFFIND4: fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
PubMed
PubMed Central
Google Scholar
Wagner, T. et al. SPHIRE-crYOLO is a fast and accurate fully automated particle picker for cryo-EM. Commun. Biol. 2, 218 (2019).
PubMed
PubMed Central
Google Scholar
Yang, Z., Fang, J., Chittuluru, J., Asturias, F. J. & Penczek, P. A. Iterative stable alignment and clustering of 2D transmission electron microscope images. Structure 20, 237–247 (2012).
CAS
PubMed
PubMed Central
Google Scholar
Moriya, T. et al. High-resolution single particle analysis from electron cryo-microscopy images using SPHIRE. J. Vis. Exp. https://doi.org/10.3791/55448 (2017).
PubMed
PubMed Central
Google Scholar
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
CAS
PubMed
Google Scholar
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).
Pettersen, E. F. et al. UCSF Chimera — a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
CAS
PubMed
Google Scholar
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Kaur, S. et al. Local computational methods to improve the interpretability and analysis of cryo-EM maps. Nat. Commun. 12, 1240 (2021).
ADS
CAS
PubMed
PubMed Central
Google Scholar
Williams, C. J. et al. MolProbity: more and better reference data for improved all-atom structure validation. Protein Sci. 27, 293–315 (2018).
CAS
PubMed
Google Scholar
Meng, E. C. et al. UCSF ChimeraX: tools for structure building and analysis. Protein Sci. 32, e4792 (2023).
CAS
PubMed
PubMed Central
Google Scholar
Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007).
CAS
PubMed
Google Scholar
Krissinel, E. Crystal contacts as nature’s docking solutions. J. Comput. Chem. 31, 133–143 (2010).
CAS
PubMed
Google Scholar
de Vries, S. J. et al. HADDOCK versus HADDOCK: new features and performance of HADDOCK2.0 on the CAPRI targets. Proteins 69, 726–733 (2007).
PubMed
Google Scholar
Dominguez, C., Boelens, R. & Bonvin, A. M. HADDOCK: a protein–protein docking approach based on biochemical or biophysical information. J. Am. Chem. Soc. 125, 1731–1737 (2003).
CAS
PubMed
Google Scholar
Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).
CAS
PubMed
Google Scholar
Sondergaard, C. R., Olsson, M. H., Rostkowski, M. & Jensen, J. H. Improved treatment of ligands and coupling effects in empirical calculation and rationalization of pKa values. J. Chem. Theory Comput. 7, 2284–2295 (2011).
CAS
PubMed
Google Scholar