{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:58:21Z","timestamp":1785351501129,"version":"3.55.0"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"31","funder":[{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["971-799"],"award-info":[{"award-number":["971-799"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP220103466"],"award-info":[{"award-number":["DP220103466"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE240100707"],"award-info":[{"award-number":["DE240100707"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1197069"],"award-info":[{"award-number":["APP1197069"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1194872"],"award-info":[{"award-number":["APP1194872"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,31]]},"abstract":"<jats:p>\n                    Heat shock protein 70 (Hsp70) and Hsp90 are essential molecular chaperones that cooperate to fold diverse client proteins, yet how their activities are coordinated to remodel clients remains unclear. To address this, we used a combination of single-molecule fluorescence resonance energy transfer and total internal reflection fluorescence microscopy to observe individual firefly luciferase proteins during sequential engagement with\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    Hsp70 (DnaK) and Hsp90 (HtpG). We show that HtpG reduces rebinding of DnaK to folding intermediates while still allowing engagement with misfolded clients, enabling productive refolding in the presence of typically inhibitory concentrations of DnaK. HtpG couples adenosine 5\u2032-triphosphate binding and hydrolysis to promote progressive folding through localized compaction across multiple regions of the client, reducing misfolding and establishing native interdomain contacts. Kinetic simulations support a model whereby heterogeneous DnaK binding generates region-specific folding kinetics and conformational dynamics. This enables efficient subdomain folding by DnaK\/HtpG and suggests that the number and position of DnaK binding sites on clients provide a mechanism by which proteins can harness chaperone promiscuity for optimal folding.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg5464","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:59:11Z","timestamp":1785347951000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Direct single-molecule visualization of Hsp90-mediated relief of an Hsp70-folding block"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8436-8683","authenticated-orcid":true,"given":"Nicholas R.","family":"Marzano","sequence":"first","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Skewes","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3227-718X","authenticated-orcid":true,"given":"Shannon","family":"McMahon","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Rice","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5345-8360","authenticated-orcid":true,"given":"Dezerae","family":"Cox","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."},{"name":"Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK."},{"name":"UK Dementia Research Institute, University of Cambridge, Cambridge CB2 0AH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-5161","authenticated-orcid":true,"given":"Antoine M.","family":"van Oijen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Sydney, G02 Jane Foss Russell Building, Sydney, NSW 2006, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-0044","authenticated-orcid":true,"given":"Heath","family":"Ecroyd","sequence":"additional","affiliation":[{"name":"Molecular Horizons and School of Science, University of Wollongong, Wollongong, NSW 2522, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02261"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.1.20"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4155\/fso.15.57"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2010.01382.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01249-0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10317"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.20"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2015.10.010"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9824036"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14245-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add0922"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.03.028"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.07.026"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.027"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583510000314"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55026-y"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2114"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2045"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35143-2"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04252-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04236-1"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111734"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.11.004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.10.004"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.11.6137"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972025p"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52674-y"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2mb25145k"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009567"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz670"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000475"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.582049"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.869027"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2144"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf5023"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.102666"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518827113"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.01.043"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"T. M. Luengo T. Ahln\u00e4s A. T. Hoekstra C. R. Berkers M. P. Mayer S. G. D. R\u00fcdiger Refolding activity of bacterial Hsp90 in vivo reveals ancient chaperoning function. bioRxiv 462549 [Preprint] (2018). https:\/\/doi.org\/10.1101\/462549.","DOI":"10.1101\/462549"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.22835"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.112110"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0SC06134D"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-05959-3"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.038"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.12.023"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2015.03.017"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.12.002"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2020-0187"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3276"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28030"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.306"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.09.020"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.082"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.24.6934"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44847-6"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.09.003"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc7002499"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3791\/50549-v"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/12\/4\/045006"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.7b12483"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphys.2004.05.017"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510496103"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(96)00033-0"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1407086111"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeg5464","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:00:16Z","timestamp":1785348016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeg5464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":64,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2026,7,31]]}},"alternative-id":["10.1126\/sciadv.aeg5464"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeg5464","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"2026-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeg5464"}}