{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:48:19Z","timestamp":1793756899324,"version":"4.6.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NRDIO\/NKFIH","award":["TKP2021-EGA-23"],"award-info":[{"award-number":["TKP2021-EGA-23"]}]},{"name":"NRDIO\/NKFIH","award":["K127961"],"award-info":[{"award-number":["K127961"]}]},{"name":"Cystic Fibrosis Foundation grant","award":["LUKACS21G0"],"award-info":[{"award-number":["LUKACS21G0"]}]},{"DOI":"10.13039\/501100002332","name":"Semmelweis University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002332","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized. The E protein is a single-pass transmembrane protein that can assemble into a pentamer forming a viroporin, perturbing Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. Because it is structurally similar to regulins such as, for example, phospholamban, that regulate the sarco\/endoplasmic reticulum calcium ATPases (SERCA), we investigated whether the SARS-CoV-2 E protein affects the SERCA system as an exoregulin. Using FRET experiments we demonstrate that E protein can form oligomers with regulins, and thus can alter the monomer\/multimer regulin ratio and consequently influence their interactions with SERCAs. We also confirm that a direct interaction between E protein and SERCA2b results in a decrease in SERCA-mediated ER Ca\n                    <jats:sup>2+<\/jats:sup>\n                    reload. Structural modeling of the complexes indicates an overlapping interaction site for E protein and endogenous regulins. Our results reveal novel links in the host-virus interaction network that play an important role in viral pathogenesis and may provide a new therapeutic target for managing severe inflammatory responses induced by SARS-CoV-2.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-71144-5","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T04:04:19Z","timestamp":1726027459000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9494-0658","authenticated-orcid":false,"given":"Blanka","family":"Berta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0875-5569","authenticated-orcid":false,"given":"Hedvig","family":"Tordai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0675","authenticated-orcid":false,"given":"Gergely L.","family":"Luk\u00e1cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5025-3087","authenticated-orcid":false,"given":"B\u00e9la","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-9376","authenticated-orcid":false,"given":"\u00c1gnes","family":"Enyedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7798-0463","authenticated-orcid":false,"given":"Rita","family":"Pad\u00e1nyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5195-749X","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Heged\u0171s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"71144_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.627278","volume":"7","author":"F Polverino","year":"2020","unstructured":"Polverino, F. & Kheradmand, F. COVID-19, COPD, and AECOPD: Immunological, epidemiological, and clinical aspects. Front. Med. 7, 627278. https:\/\/doi.org\/10.3389\/fmed.2020.627278 (2020).","journal-title":"Front. Med."},{"key":"71144_CR2","doi-asserted-by":"publisher","first-page":"L39","DOI":"10.1529\/biophysj.108.133041","volume":"95","author":"K Parthasarathy","year":"2008","unstructured":"Parthasarathy, K. et al. Structural flexibility of the pentameric SARS coronavirus envelope protein ion channel. Biophys. J. 95, L39\u2013L41. https:\/\/doi.org\/10.1529\/biophysj.108.133041 (2008).","journal-title":"Biophys. J."},{"key":"71144_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/B978-0-12-385885-6.00009-2","volume":"81","author":"SR Weiss","year":"2011","unstructured":"Weiss, S. R. & Leibowitz, J. L. Coronavirus pathogenesis. Adv. Virus Res. 81, 85\u2013164. https:\/\/doi.org\/10.1016\/B978-0-12-385885-6.00009-2 (2011).","journal-title":"Adv. Virus Res."},{"key":"71144_CR4","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/s41422-021-00519-4","volume":"31","author":"B Xia","year":"2021","unstructured":"Xia, B. et al. SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target. Cell Res. 31, 847\u2013860. https:\/\/doi.org\/10.1038\/s41422-021-00519-4 (2021).","journal-title":"Cell Res."},{"key":"71144_CR5","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.virol.2015.02.005","volume":"478","author":"P Venkatagopalan","year":"2015","unstructured":"Venkatagopalan, P. et al. Coronavirus envelope (E) protein remains at the site of assembly. Virology 478, 75\u201385. https:\/\/doi.org\/10.1016\/j.virol.2015.02.005 (2015).","journal-title":"Virology"},{"key":"71144_CR6","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/s42003-021-02250-7","volume":"4","author":"A Javorsky","year":"2021","unstructured":"Javorsky, A., Humbert, P. O. & Kvansakul, M. Structural basis of coronavirus E protein interactions with human PALS1 PDZ domain. Commun. Biol. 4, 724. https:\/\/doi.org\/10.1038\/s42003-021-02250-7 (2021).","journal-title":"Commun. Biol."},{"key":"71144_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004320","volume":"10","author":"JM Jimenez-Guarde\u00f1o","year":"2014","unstructured":"Jimenez-Guarde\u00f1o, J. M. et al. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. PLoS Pathog. 10, e1004320. https:\/\/doi.org\/10.1371\/journal.ppat.1004320 (2014).","journal-title":"PLoS Pathog."},{"key":"71144_CR8","doi-asserted-by":"publisher","first-page":"13285","DOI":"10.3390\/ijms232113285","volume":"23","author":"W Surya","year":"2022","unstructured":"Surya, W. & Torres, J. Oligomerization-dependent beta-structure formation in SARS-CoV-2 envelope protein. Int. J. Mol. Sci. 23, 13285. https:\/\/doi.org\/10.3390\/ijms232113285 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"71144_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.167966","volume":"435","author":"AJ Dregni","year":"2023","unstructured":"Dregni, A. J. et al. The cytoplasmic domain of the SARS-CoV-2 envelope protein assembles into a \u03b2-sheet bundle in lipid bilayers. J. Mol. Biol. 435, 167966. https:\/\/doi.org\/10.1016\/j.jmb.2023.167966 (2023).","journal-title":"J. Mol. Biol."},{"key":"71144_CR10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009519","volume":"17","author":"SH Park","year":"2021","unstructured":"Park, S. H. et al. Interactions of SARS-CoV-2 envelope protein with amilorides correlate with antiviral activity. PLoS Pathog. 17, e1009519. https:\/\/doi.org\/10.1371\/journal.ppat.1009519 (2021).","journal-title":"PLoS Pathog."},{"key":"71144_CR11","doi-asserted-by":"publisher","first-page":"D434","DOI":"10.1093\/nar\/gkad928","volume":"52","author":"MC Aspromonte","year":"2024","unstructured":"Aspromonte, M. C. et al. DisProt in 2024: Improving function annotation of intrinsically disordered proteins. Nucleic Acids Res. 52, D434\u2013D441. https:\/\/doi.org\/10.1093\/nar\/gkad928 (2024).","journal-title":"Nucleic Acids Res."},{"key":"71144_CR12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.virol.2011.03.029","volume":"415","author":"JL Nieto-Torres","year":"2011","unstructured":"Nieto-Torres, J. L. et al. Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein. Virology 415, 69\u201382. https:\/\/doi.org\/10.1016\/j.virol.2011.03.029 (2011).","journal-title":"Virology"},{"key":"71144_CR13","doi-asserted-by":"publisher","first-page":"12454","DOI":"10.3390\/ijms241512454","volume":"24","author":"W Surya","year":"2023","unstructured":"Surya, W. et al. The complex proteolipidic behavior of the SARS-CoV-2 envelope protein channel: Weak selectivity and heterogeneous oligomerization. Int. J. Mol. Sci. 24, 12454. https:\/\/doi.org\/10.3390\/ijms241512454 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"71144_CR14","doi-asserted-by":"publisher","first-page":"4733","DOI":"10.1021\/cr900013m","volume":"109","author":"P Vangheluwe","year":"2009","unstructured":"Vangheluwe, P. et al. Intracellular Ca2+- and Mn2+-transport ATPases. Chem. Rev. 109, 4733\u20134759. https:\/\/doi.org\/10.1021\/cr900013m (2009).","journal-title":"Chem. Rev."},{"key":"71144_CR15","doi-asserted-by":"publisher","first-page":"4429","DOI":"10.1016\/j.jmb.2019.07.037","volume":"431","author":"DR Singh","year":"2019","unstructured":"Singh, D. R. et al. Newly discovered micropeptide regulators of SERCA form oligomers but bind to the pump as monomers. J. Mol. Biol. 431, 4429\u20134443. https:\/\/doi.org\/10.1016\/j.jmb.2019.07.037 (2019).","journal-title":"J. Mol. Biol."},{"key":"71144_CR16","doi-asserted-by":"publisher","first-page":"e00217","DOI":"10.1128\/JVI.00217-21","volume":"95","author":"J Peng","year":"2021","unstructured":"Peng, J. et al. Sarco\/endoplasmic reticulum Ca2+ transporting ATPase (SERCA) modulates autophagic, inflammatory, and mitochondrial responses during influenza A virus infection in human lung cells. J. Virol. 95, e00217-21. https:\/\/doi.org\/10.1128\/JVI.00217-21 (2021).","journal-title":"J. Virol."},{"key":"71144_CR17","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3389\/fmicb.2019.00209","volume":"10","author":"N Kumar","year":"2019","unstructured":"Kumar, N. et al. Inhibitor of sarco\/endoplasmic reticulum calcium-ATPase impairs multiple steps of paramyxovirus replication. Front. Microbiol. 10, 209. https:\/\/doi.org\/10.3389\/fmicb.2019.00209 (2019).","journal-title":"Front. Microbiol."},{"key":"71144_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2022.105464","volume":"209","author":"D Ojha","year":"2023","unstructured":"Ojha, D., Basu, R. & Peterson, K. E. Therapeutic targeting of organelles for inhibition of Zika virus replication in neurons. Antiviral Res. 209, 105464. https:\/\/doi.org\/10.1016\/j.antiviral.2022.105464 (2023).","journal-title":"Antiviral Res."},{"key":"71144_CR19","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1006\/geno.1997.4967","volume":"45","author":"A Odermatt","year":"1997","unstructured":"Odermatt, A. et al. Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: Absence of structural mutations in five patients with Brody disease. Genomics 45, 541\u2013553. https:\/\/doi.org\/10.1006\/geno.1997.4967 (1997).","journal-title":"Genomics"},{"key":"71144_CR20","doi-asserted-by":"publisher","first-page":"8891","DOI":"10.3390\/ijms22168891","volume":"22","author":"N Rathod","year":"2021","unstructured":"Rathod, N. et al. Nothing regular about the regulins: Distinct functional properties of SERCA transmembrane peptide regulatory subunits. Int. J. Mol. Sci. 22, 8891. https:\/\/doi.org\/10.3390\/ijms22168891 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"71144_CR21","doi-asserted-by":"publisher","first-page":"ra119","DOI":"10.1126\/scisignal.aaj1460","volume":"9","author":"DM Anderson","year":"2016","unstructured":"Anderson, D. M. et al. Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides. Sci. Signal 9, ra119. https:\/\/doi.org\/10.1126\/scisignal.aaj1460 (2016).","journal-title":"Sci. Signal"},{"key":"71144_CR22","doi-asserted-by":"publisher","first-page":"D355","DOI":"10.1093\/nar\/gkaa954","volume":"49","author":"G Csizmadia","year":"2021","unstructured":"Csizmadia, G. et al. The MemMoRF database for recognizing disordered protein regions interacting with cellular membranes. Nucleic Acids Res. 49, D355\u2013D360. https:\/\/doi.org\/10.1093\/nar\/gkaa954 (2021).","journal-title":"Nucleic Acids Res."},{"key":"71144_CR23","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1021\/bi961955q","volume":"36","author":"RL Cornea","year":"1997","unstructured":"Cornea, R. L., Jones, L. R., Autry, J. M. & Thomas, D. D. Mutation and phosphorylation change the oligomeric structure of phospholamban in lipid bilayers. Biochemistry 36, 2960\u20132967. https:\/\/doi.org\/10.1021\/bi961955q (1997).","journal-title":"Biochemistry"},{"key":"71144_CR24","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.bpj.2022.12.014","volume":"122","author":"TA Phillips","year":"2023","unstructured":"Phillips, T. A. et al. Micropeptide hetero-oligomerization adds complexity to the calcium pump regulatory network. Biophys. J. 122, 301\u2013309. https:\/\/doi.org\/10.1016\/j.bpj.2022.12.014 (2023).","journal-title":"Biophys. J."},{"key":"71144_CR25","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.virol.2006.01.028","volume":"349","author":"Y Liao","year":"2006","unstructured":"Liao, Y. et al. Biochemical and functional characterization of the membrane association and membrane permeabilizing activity of the severe acute respiratory syndrome coronavirus envelope protein. Virology 349, 264\u2013275. https:\/\/doi.org\/10.1016\/j.virol.2006.01.028 (2006).","journal-title":"Virology"},{"key":"71144_CR26","doi-asserted-by":"publisher","DOI":"10.1113\/JP284179","author":"R Naffa","year":"2023","unstructured":"Naffa, R. et al. Plasma membrane Ca2+ pump isoform 4 function in cell migration and cancer metastasis. J. Physiol. https:\/\/doi.org\/10.1113\/JP284179 (2023).","journal-title":"J. Physiol."},{"key":"71144_CR27","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.csbj.2021.12.031","volume":"20","author":"AY Liu","year":"2022","unstructured":"Liu, A. Y. et al. Homologous cardiac calcium pump regulators phospholamban and sarcolipin adopt distinct oligomeric states in the membrane. Comput. Struct. Biotechnol. J. 20, 380\u2013384. https:\/\/doi.org\/10.1016\/j.csbj.2021.12.031 (2022).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"71144_CR28","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.neuron.2017.01.010","volume":"93","author":"J de Juan-Sanz","year":"2017","unstructured":"de Juan-Sanz, J. et al. Axonal endoplasmic reticulum Ca2+ content controls release probability in CNS nerve terminals. Neuron 93, 867-881.e6. https:\/\/doi.org\/10.1016\/j.neuron.2017.01.010 (2017).","journal-title":"Neuron"},{"key":"71144_CR29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12985-019-1182-0","volume":"16","author":"D Schoeman","year":"2019","unstructured":"Schoeman, D. & Fielding, B. C. Coronavirus envelope protein: current knowledge. Virol. J. 16, 69. https:\/\/doi.org\/10.1186\/s12985-019-1182-0 (2019).","journal-title":"Virol. J."},{"key":"71144_CR30","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ceca.2017.07.001","volume":"69","author":"ER Chemaly","year":"2018","unstructured":"Chemaly, E. R., Troncone, L. & Lebeche, D. SERCA control of cell death and survival. Cell Calcium 69, 46\u201361. https:\/\/doi.org\/10.1016\/j.ceca.2017.07.001 (2018).","journal-title":"Cell Calcium"},{"key":"71144_CR31","doi-asserted-by":"publisher","first-page":"ra19","DOI":"10.1126\/scisignal.2005672","volume":"8","author":"K P\u00e1szty","year":"2015","unstructured":"P\u00e1szty, K. et al. Plasma membrane Ca2+-ATPases can shape the pattern of Ca2+ transients induced by store-operated Ca2+ entry. Sci. Signal 8, ra19. https:\/\/doi.org\/10.1126\/scisignal.2005672 (2015).","journal-title":"Sci. Signal"},{"key":"71144_CR32","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/s41419-023-05817-w","volume":"14","author":"E Poggio","year":"2023","unstructured":"Poggio, E. et al. Perturbation of the host cell Ca2+ homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M. Cell Death Dis. 14, 297. https:\/\/doi.org\/10.1038\/s41419-023-05817-w (2023).","journal-title":"Cell Death Dis."},{"key":"71144_CR33","doi-asserted-by":"publisher","unstructured":"Samavarchi-Tehrani, P., Abdouni, H., Knight, J. D. R., et al. A SARS-CoV-2\u2014Host proximity interactome. bioRxiv https:\/\/doi.org\/10.1101\/2020.09.03.282103 (2020).","DOI":"10.1101\/2020.09.03.282103"},{"key":"71144_CR34","doi-asserted-by":"publisher","first-page":"103562","DOI":"10.1016\/j.isci.2021.103562","volume":"25","author":"S Nabeel-Shah","year":"2022","unstructured":"Nabeel-Shah, S. et al. SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenuates stress granules to impair host stress response. iScience 25, 103562. https:\/\/doi.org\/10.1016\/j.isci.2021.103562 (2022).","journal-title":"iScience"},{"key":"71144_CR35","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.tim.2004.12.005","volume":"13","author":"FJM van Kuppeveld","year":"2005","unstructured":"van Kuppeveld, F. J. M., de Jong, A. S., Melchers, W. J. G. & Willems, P. H. G. M. Enterovirus protein 2B po(u)res out the calcium: A viral strategy to survive?. Trends Microbiol. 13, 41\u201344. https:\/\/doi.org\/10.1016\/j.tim.2004.12.005 (2005).","journal-title":"Trends Microbiol."},{"key":"71144_CR36","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/j.cell.2019.01.034","volume":"176","author":"J Kominek","year":"2019","unstructured":"Kominek, J. et al. Eukaryotic acquisition of a bacterial operon. Cell 176, 1356-1366.e10. https:\/\/doi.org\/10.1016\/j.cell.2019.01.034 (2019).","journal-title":"Cell"},{"key":"71144_CR37","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-2508369\/v1","author":"SR Zack","year":"2023","unstructured":"Zack, S. R. et al. Vacuole membrane protein 1 (VMP1) restricts NLRP3 inflammasome activation by modulating SERCA activity and autophagy. Res. Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-2508369\/v1 (2023).","journal-title":"Res. Sq."},{"key":"71144_CR38","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.molcel.2017.08.005","volume":"67","author":"YG Zhao","year":"2017","unstructured":"Zhao, Y. G. et al. The ER-localized transmembrane protein EPG-3\/VMP1 regulates SERCA activity to control ER-isolation membrane contacts for autophagosome formation. Mol. Cell 67, 974-989.e6. https:\/\/doi.org\/10.1016\/j.molcel.2017.08.005 (2017).","journal-title":"Mol. Cell"},{"key":"71144_CR39","doi-asserted-by":"publisher","unstructured":"St-Germain, J. R., Astori, A., Samavarchi-Tehrani, P., et al. A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research. bioRxiv  https:\/\/doi.org\/10.1101\/2020.08.28.269175 (2020)","DOI":"10.1101\/2020.08.28.269175"},{"key":"71144_CR40","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.bbrc.2007.05.180","volume":"359","author":"D Stepensky","year":"2007","unstructured":"Stepensky, D. FRETcalc plugin for calculation of FRET in non-continuous intracellular compartments. Biochem. Biophys. Res. Commun. 359, 752\u2013758. https:\/\/doi.org\/10.1016\/j.bbrc.2007.05.180 (2007).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"71144_CR41","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/S0076-6879(03)74020-8","volume":"374","author":"A Fiser","year":"2003","unstructured":"Fiser, A. & Sali, A. Modeller: Generation and refinement of homology-based protein structure models. Methods Enzymol. 374, 461\u2013491. https:\/\/doi.org\/10.1016\/S0076-6879(03)74020-8 (2003).","journal-title":"Methods Enzymol."},{"key":"71144_CR42","doi-asserted-by":"publisher","first-page":"8877","DOI":"10.3390\/ijms23168877","volume":"23","author":"H Tordai","year":"2022","unstructured":"Tordai, H. et al. Comprehensive collection and prediction of ABC transmembrane protein structures in the AI era of structural biology. Int. J. Mol. Sci. 23, 8877. https:\/\/doi.org\/10.3390\/ijms23168877 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"71144_CR43","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s00018-021-04112-1","volume":"79","author":"T Heged\u0171s","year":"2022","unstructured":"Heged\u0171s, T., Geisler, M., Luk\u00e1cs, G. L. & Farkas, B. Ins and outs of AlphaFold2 transmembrane protein structure predictions. Cell. Mol. Life Sci. 79, 73. https:\/\/doi.org\/10.1007\/s00018-021-04112-1 (2022).","journal-title":"Cell. Mol. Life Sci."},{"key":"71144_CR44","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","volume":"29","author":"S Jo","year":"2008","unstructured":"Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: A web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859\u20131865. https:\/\/doi.org\/10.1002\/jcc.20945 (2008).","journal-title":"J. Comput. Chem."},{"key":"71144_CR45","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/jcc.23702","volume":"35","author":"EL Wu","year":"2014","unstructured":"Wu, E. L. et al. CHARMM-GUI membrane builder toward realistic biological membrane simulations. J. Comput. Chem. 35, 1997\u20132004. https:\/\/doi.org\/10.1002\/jcc.23702 (2014).","journal-title":"J. Comput. Chem."},{"key":"71144_CR46","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1093\/bioinformatics\/btk023","volume":"22","author":"MA Lomize","year":"2006","unstructured":"Lomize, M. A., Lomize, A. L., Pogozheva, I. D. & Mosberg, H. I. OPM: Orientations of proteins in membranes database. Bioinformatics 22, 623\u2013625. https:\/\/doi.org\/10.1093\/bioinformatics\/btk023 (2006).","journal-title":"Bioinformatics"},{"key":"71144_CR47","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","volume":"14","author":"J Huang","year":"2017","unstructured":"Huang, J. et al. CHARMM36m: An improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71\u201373. https:\/\/doi.org\/10.1038\/nmeth.4067 (2017).","journal-title":"Nat. Methods"},{"key":"71144_CR48","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jcc.20291","volume":"26","author":"D Van Der Spoel","year":"2005","unstructured":"Van Der Spoel, D. et al. GROMACS: Fast, flexible, and free. J. Comput. Chem. 26, 1701\u20131718. https:\/\/doi.org\/10.1002\/jcc.20291 (2005).","journal-title":"J. Comput. Chem."},{"key":"71144_CR49","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1002\/jcc.21787","volume":"32","author":"N Michaud-Agrawal","year":"2011","unstructured":"Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: A toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319\u20132327. https:\/\/doi.org\/10.1002\/jcc.21787 (2011).","journal-title":"J. Comput. Chem."},{"key":"71144_CR50","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","volume":"9","author":"JD Hunter","year":"2007","unstructured":"Hunter, J. D. Matplotlib: A 2D graphics environment. Comput. Sci. Eng. 9, 90\u201395. https:\/\/doi.org\/10.1109\/MCSE.2007.55 (2007).","journal-title":"Comput. Sci. Eng."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71144-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71144-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71144-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T04:08:59Z","timestamp":1726027739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-71144-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["71144"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-71144-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.13.544745","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,11]]},"assertion":[{"value":"6 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"During the preparation of this work the author(s) used ChatGPT in order to enhance English language proficiency. After using this tool\/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21200"}}