[{"month":"06","title":"Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo","date_published":"2026-06-22T00:00:00Z","acknowledgement":"We thank IST Austria for providing the funding. We thank IST Austria EM facility for the use of Titan Krios TEM. Data processing was performed using IST high-performance computer cluster. We thank Dr. R. Roemhild and Professor C. Guet (ISTA) for help in constructing Tat deletion strains and Dr. A. Charnagalov (ISTA) for technical help.","year":"2026","type":"journal_article","article_type":"original","ddc":["570"],"OA_type":"hybrid","license":"https://creativecommons.org/licenses/by-nc/4.0/","publication":"Molecular Cell","day":"22","publication_identifier":{"eissn":["1097-4164"],"issn":["1097-2765"]},"oa":1,"quality_controlled":"1","publication_status":"inpress","publisher":"Elsevier","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","researchdata_availability":"yes","abstract":[{"lang":"eng","text":"How the twin-arginine translocase (Tat) system transports fully folded substrate proteins across cellular membranes without disrupting membrane integrity has been a fundamental question in cell biology for decades. The Tat system, found in prokaryotes and plant organelles, recognizes a cargo signal peptide via a conserved twin-arginine motif. The multi-subunit Tat complex facilitates the proton-motive-force-dependent translocation process, yet its overall architecture has remained unknown. Here, we present the cryo-electron microscopy (cryo-EM) structure of the Escherichia coli (E. coli) trimeric TatB₃C₃ complex with bound substrate SufI, assembled in vivo. The complex adopts an unusual, wide-open, bowl-shaped architecture with a polar inner cavity. Unexpectedly, the cargo is engaged in a dual-contact mode: while the signal peptide binds inside one TatBC unit, the folded domain docks tightly onto an adjacent unit, possibly performing a proofreading function. This structure provides a mechanistic framework for substrate engagement and suggests the direct involvement of the entire Tat complex in substrate translocation."}],"corr_author":"1","citation":{"ieee":"Z. Zhao and L. A. Sazanov, “Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo,” <i>Molecular Cell</i>. Elsevier.","chicago":"Zhao, Ziyu, and Leonid A Sazanov. “Structure of E. Coli Twin-Arginine Translocase (Tat) Complex with Bound Cargo.” <i>Molecular Cell</i>. Elsevier, n.d. <a href=\"https://doi.org/10.1016/j.molcel.2026.05.026\">https://doi.org/10.1016/j.molcel.2026.05.026</a>.","mla":"Zhao, Ziyu, and Leonid A. Sazanov. “Structure of E. Coli Twin-Arginine Translocase (Tat) Complex with Bound Cargo.” <i>Molecular Cell</i>, Elsevier, doi:<a href=\"https://doi.org/10.1016/j.molcel.2026.05.026\">10.1016/j.molcel.2026.05.026</a>.","apa":"Zhao, Z., &#38; Sazanov, L. A. (n.d.). Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo. <i>Molecular Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.molcel.2026.05.026\">https://doi.org/10.1016/j.molcel.2026.05.026</a>","ista":"Zhao Z, Sazanov LA. Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo. Molecular Cell.","short":"Z. Zhao, L.A. Sazanov, Molecular Cell (n.d.).","ama":"Zhao Z, Sazanov LA. Structure of E. Coli twin-arginine translocase (Tat) complex with bound cargo. <i>Molecular Cell</i>. doi:<a href=\"https://doi.org/10.1016/j.molcel.2026.05.026\">10.1016/j.molcel.2026.05.026</a>"},"related_material":{"link":[{"url":"https://ista.ac.at/en/news/the-gate-for-bulky-cargo/","relation":"press_release","description":"News on ISTA website"}],"record":[{"relation":"research_data","status":"public","id":"22189"}]},"supplementarymaterial":"yes","author":[{"id":"a63fe682-9f3a-11ee-bf8c-cfdf919b9850","first_name":"Ziyu","last_name":"Zhao","full_name":"Zhao, Ziyu"},{"full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87"}],"das_tickbox":"1","external_id":{"biorxivid":["10.1101/2025.09.16.676506"]},"fulldoi":"https://doi.org/10.1016/j.molcel.2026.05.026","oa_version":"Published Version","language":[{"iso":"eng"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.molcel.2026.05.026"}],"has_accepted_license":"1","date_created":"2026-06-28T22:01:35Z","doi":"10.1016/j.molcel.2026.05.026","_id":"22148","article_processing_charge":"Yes (via OA deal)","date_updated":"2026-08-12T12:08:44Z","biorxivid":1,"scopus_import":"1","OA_place":"publisher","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"ScienComp"}],"status":"public","dataavailabilitystatement":"This study did not generate new unique reagents. Strains and plasmids generated in this study are available from the lead contact without restrictions.\r\n• Source data are provided within this paper. The cryo-EM map is deposited in the Electron Microscopy Data Bank under accession number EMD-53848. The model is deposited in the Protein Data Bank under accession number 9R91. The structural data are publicly available as of the date of publication. Raw images of spot assays, SDS-PAGE and BN-PAGE gels with Coomassie staining and immunoblot images are available at Mendeley Data (https://doi.org/10.17632/v2g3p9n985.1).\r\n• This paper does not report original code.\r\n• Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png"},"department":[{"_id":"LeSa"}]},{"_id":"22750","doi":"10.1038/s41467-026-75324-x","article_processing_charge":"Yes","date_updated":"2026-09-07T13:17:53Z","scopus_import":"1","status":"public","dataavailabilitystatement":"The cryo-EM maps are deposited in the Electron Microscopy Data Bank under accession number EMD- 51100 (inactive dimer), EMD- 51102 (active dimer) and EMD-51101 (semi-active dimer). The models are deposited in the Protein Data Bank under accession numbers 9G6F (inactive dimer), 9G6H (active dimer) and 9G6G (semi-active dimer). Mass spectrometry data was uploaded to MassIVE with accession code MSV000101057. Source data are provided with this paper.","OA_place":"publisher","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"department":[{"_id":"LeSa"}],"article_number":"8433","das_tickbox":"1","volume":17,"fulldoi":"https://doi.org/10.1038/s41467-026-75324-x","external_id":{"pmid":["42420307"]},"language":[{"iso":"eng"}],"oa_version":"Published Version","has_accepted_license":"1","date_created":"2026-08-23T22:01:46Z","publication_identifier":{"eissn":["2041-1723"]},"oa":1,"quality_controlled":"1","publication_status":"published","publisher":"Springer Nature","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"corr_author":"1","researchdata_availability":"yes","abstract":[{"text":"Robust oxygenic photosynthesis requires the efficient assembly and repair of the multi-subunit oxygen-evolving photosystem II (PSII) complex. Previous cryogenic electron microscopy (cryo-EM) structures of PSII assembly/disassembly intermediates have relied on the analysis of deletion mutants or removal of PSII subunits in vitro. Here we report the cryo-EM structures of naturally occurring dimeric PSII intermediates from the cyanobacterium Thermosynechococcus vestitus at a resolution of about 2.2 Å. These intermediates contain inactive dimers lacking the oxygen-evolving complex (OEC) and semi-active dimers with the OEC present in one of the two monomers. Our structural data provide a mechanism for how assembly and disassembly of the Mn4CaO5 cluster is coordinated with the binding and release of the extrinsic proteins: restructuring of the C-terminal tail of D1 subunit during assembly or disassembly of the Mn cluster triggers conformational changes in D2, CP47 and CP43 to drive the binding/release of the extrinsic proteins. A combination of structural and mass spectrometry data also suggests that the inactive PSII complexes may include damaged complexes containing oxidized D1-His332, a monodentate ligand to one of the Mn ions of the OEC.","lang":"eng"}],"author":[{"last_name":"Zhao","full_name":"Zhao, Ziyu","id":"a63fe682-9f3a-11ee-bf8c-cfdf919b9850","first_name":"Ziyu"},{"id":"3ED6AF16-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5618-3449","first_name":"Irene","last_name":"Vercellino","full_name":"Vercellino, Irene"},{"full_name":"Whitelegge, Julian P.","last_name":"Whitelegge","first_name":"Julian P."},{"last_name":"Maghlaoui","full_name":"Maghlaoui, Karim","first_name":"Karim"},{"first_name":"Wojciech","full_name":"Białek, Wojciech","last_name":"Białek"},{"first_name":"Peter J.","last_name":"Nixon","full_name":"Nixon, Peter J."},{"full_name":"Sazanov, Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","first_name":"Leonid A"}],"supplementarymaterial":"yes","DOAJ_listed":"1","file_date_updated":"2026-09-07T13:13:03Z","citation":{"chicago":"Zhao, Ziyu, Irene Vercellino, Julian P. Whitelegge, Karim Maghlaoui, Wojciech Białek, Peter J. Nixon, and Leonid A Sazanov. “Cryo-EM Structures of Naturally Occurring Dimeric Photosystem II Complexes Lacking the Mn4CaO5 Cluster.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-75324-x\">https://doi.org/10.1038/s41467-026-75324-x</a>.","ieee":"Z. Zhao <i>et al.</i>, “Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn4CaO5 cluster,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","mla":"Zhao, Ziyu, et al. “Cryo-EM Structures of Naturally Occurring Dimeric Photosystem II Complexes Lacking the Mn4CaO5 Cluster.” <i>Nature Communications</i>, vol. 17, 8433, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-75324-x\">10.1038/s41467-026-75324-x</a>.","apa":"Zhao, Z., Vercellino, I., Whitelegge, J. P., Maghlaoui, K., Białek, W., Nixon, P. J., &#38; Sazanov, L. A. (2026). Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn4CaO5 cluster. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-75324-x\">https://doi.org/10.1038/s41467-026-75324-x</a>","ista":"Zhao Z, Vercellino I, Whitelegge JP, Maghlaoui K, Białek W, Nixon PJ, Sazanov LA. 2026. Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn4CaO5 cluster. Nature Communications. 17, 8433.","ama":"Zhao Z, Vercellino I, Whitelegge JP, et al. Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn4CaO5 cluster. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-75324-x\">10.1038/s41467-026-75324-x</a>","short":"Z. Zhao, I. Vercellino, J.P. Whitelegge, K. Maghlaoui, W. Białek, P.J. Nixon, L.A. Sazanov, Nature Communications 17 (2026)."},"month":"08","title":"Cryo-EM structures of naturally occurring dimeric photosystem II complexes lacking the Mn4CaO5 cluster","acknowledgement":"P.J.N. is grateful for the support from the Imperial College Electron Microscopy Center. L.A.S. acknowledges the support from the Scientific Service Units (SSU) of IST Austria: the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. P.J.N. is grateful for the support of the Biotechnology & Biological Sciences Research Council (awards BB/I00937X/1, BB/L003260/1 and BB/P00931X/1). L.A.S. is grateful to IST Austria for providing the funding.","file":[{"file_size":3370665,"content_type":"application/pdf","date_updated":"2026-09-07T13:13:03Z","file_name":"2026_NatureComm_Zhao.pdf","checksum":"a820b736585de22bcfa30ebdd25a6dd2","file_id":"22843","success":1,"relation":"main_file","date_created":"2026-09-07T13:13:03Z","creator":"dernst","access_level":"open_access"}],"date_published":"2026-08-17T00:00:00Z","year":"2026","intvolume":"        17","article_type":"original","type":"journal_article","OA_type":"gold","ddc":["570"],"day":"17","publication":"Nature Communications"}]