{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:14:19Z","timestamp":1788254059640,"version":"build-2803163510"},"reference-count":48,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01-BX006371-01"],"award-info":[{"award-number":["I01-BX006371-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01-DK116780"],"award-info":[{"award-number":["R01-DK116780"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.jbc.2025.110913","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T16:50:23Z","timestamp":1762361423000},"page":"110913","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rewiring PTH receptor signaling: Hormone dimerization restores endosomal signaling lost in hypocalcemia-linked PTH mutant"],"prefix":"10.1016","volume":"301","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-5874","authenticated-orcid":false,"given":"Jonathan","family":"Pacheco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8032-6861","authenticated-orcid":false,"given":"Satyaki","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-6963","authenticated-orcid":false,"given":"Ji Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8075-4782","authenticated-orcid":false,"given":"Kelly J.","family":"Culhane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-4176","authenticated-orcid":false,"given":"Ivet","family":"Bahar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-1435","authenticated-orcid":false,"given":"Jean-Pierre","family":"Vilardaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2025.110913_bib1","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1210\/endrev\/bnac032","article-title":"Molecular mechanisms of PTH\/PTHrP class B GPCR signaling and pharmacological implications","volume":"44","author":"Vilardaga","year":"2023","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.jbc.2025.110913_bib2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nchembio.206","article-title":"Sustained cyclic AMP production by parathyroid hormone receptor endocytosis","volume":"5","author":"Ferrandon","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib3","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.abc5944","article-title":"Spatial bias in cAMP generation determines biological responses to PTH type 1 receptor activation","volume":"14","author":"White","year":"2021","journal-title":"Sci. Signal."},{"key":"10.1016\/j.jbc.2025.110913_bib4","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/jbmr.2532","article-title":"A homozygous [Cys25]PTH(1-84) mutation that impairs PTH\/PTHrP receptor activation defines a novel form of hypoparathyroidism","volume":"30","author":"Lee","year":"2015","journal-title":"J. Bone Miner Res."},{"key":"10.1016\/j.jbc.2025.110913_bib5","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1073\/pnas.1814670116","article-title":"Ca(2+) allostery in PTH-receptor signaling","volume":"116","author":"White","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2025.110913_bib6","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1210\/endo-123-6-2611","article-title":"Structural properties of the renal parathyroid hormone receptor: hydrodynamic analysis and protease sensitivity","volume":"123","author":"Karpf","year":"1988","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.110913_bib7","doi-asserted-by":"crossref","first-page":"12435","DOI":"10.1074\/jbc.M109.093138","article-title":"Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation","volume":"285","author":"Pioszak","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2025.110913_bib8","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/ncb2022","article-title":"TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling","volume":"12","author":"Qiu","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib9","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nchembio.2286","article-title":"HTS-compatible FRET-based conformational sensors clarify membrane receptor activation","volume":"13","author":"Scholler","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib10","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-biophys-070816-033834","article-title":"Weighted ensemble simulation: review of methodology, applications, and software","volume":"46","author":"Zuckerman","year":"2017","journal-title":"Annu. Rev. Biophys."},{"key":"10.1016\/j.jbc.2025.110913_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-54772-3","article-title":"Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone-GPCR-arrestin complex","volume":"15","author":"Pacheco","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2025.110913_bib12","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1083\/jcb.143.2.501","article-title":"Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools","volume":"143","author":"Varnai","year":"1998","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib13","doi-asserted-by":"crossref","first-page":"17167","DOI":"10.1074\/jbc.M113.464065","article-title":"Detection of G protein-selective G protein-coupled receptor (GPCR) conformations in live cells","volume":"288","author":"Malik","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2025.110913_bib14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nchembio705","article-title":"Molecular basis of inverse agonism in a G protein-coupled receptor","volume":"1","author":"Vilardaga","year":"2005","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib15","article-title":"Dimeric R25CPTH(1-34) activates the parathyroid Hormone-1 receptor in vitro and stimulates bone Formation in osteoporotic female mice","volume":"13","author":"Minsoo Noh","year":"2024","journal-title":"eLife"},{"key":"10.1016\/j.jbc.2025.110913_bib16","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.93830","article-title":"Enhancing bone regeneration and osseointegration using rhPTH(1-34) and dimeric (R25C)PTH(1-34) in an osteoporotic beagle model","volume":"13","author":"Shin","year":"2024","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2025.110913_bib17","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1126\/science.aav7942","article-title":"Structure and dynamics of the active human parathyroid hormone receptor-1","volume":"364","author":"Zhao","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.jbc.2025.110913_bib18","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1073\/pnas.1221585110","article-title":"Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations","volume":"110","author":"Wootten","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2025.110913_bib19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1124\/molpharm.121.000400","article-title":"Allosteric Modulator KM822 Attenuates behavioral actions of amphetamine in Caenorhabditis elegans through interactions with the dopamine transporter DAT-1","volume":"101","author":"Refai","year":"2022","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.jbc.2025.110913_bib20","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s41589-021-00929-w","article-title":"Precise druggability of the PTH type 1 receptor","volume":"18","author":"Sutkeviciute","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib21","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nbt838","article-title":"Measurement of the millisecond activation switch of G protein-coupled receptors in living cells","volume":"21","author":"Vilardaga","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jbc.2025.110913_bib22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.tips.2022.01.002","article-title":"Structural perspective of class B1 GPCR signaling","volume":"43","author":"Cong","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.jbc.2025.110913_bib23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.tips.2011.05.006","article-title":"Asymmetry of GPCR oligomers supports their functional relevance","volume":"32","author":"Maurice","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.jbc.2025.110913_bib24","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.tibs.2010.05.002","article-title":"Oligomeric forms of G protein-coupled receptors (GPCRs)","volume":"35","author":"Palczewski","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.jbc.2025.110913_bib25","doi-asserted-by":"crossref","first-page":"4390","DOI":"10.1038\/s41467-024-48853-6","article-title":"Impact of secretin receptor homo-dimerization on natural ligand binding","volume":"15","author":"Harikumar","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2025.110913_bib26","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s41589-020-0567-0","article-title":"Allosteric interactions in the parathyroid hormone GPCR-arrestin complex formation","volume":"16","author":"Clark","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jbc.2025.110913_bib27","doi-asserted-by":"crossref","first-page":"3854","DOI":"10.1210\/en.2002-220232","article-title":"Dual regulation of the parathyroid hormone (PTH)\/PTH-related peptide receptor signaling by protein kinase C and beta-arrestins","volume":"143","author":"Castro","year":"2002","journal-title":"Endocrinology"},{"key":"10.1016\/j.jbc.2025.110913_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.102332","article-title":"Biased GPCR signaling by the native parathyroid hormone-related protein 1 to 141 relative to its N-terminal fragment 1 to 36","volume":"298","author":"Pena","year":"2022","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2025.110913_bib29","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1073\/pnas.1205756110","article-title":"Noncanonical GPCR signaling arising from a PTH receptor-arrestin-gbetagamma complex","volume":"110","author":"Wehbi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2025.110913_bib30","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.261494","article-title":"A novel homeostatic mechanism tunes PI(4,5)P2-dependent signaling at the plasma membrane","volume":"136","author":"Wills","year":"2023","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.jbc.2025.110913_bib31","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1093\/bioinformatics\/btu202","article-title":"ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging","volume":"30","author":"Ovesny","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jbc.2025.110913_bib32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ymeth.2016.09.016","article-title":"TrackMate: an open and extensible platform for single-particle tracking","volume":"115","author":"Tinevez","year":"2017","journal-title":"Methods"},{"key":"10.1016\/j.jbc.2025.110913_bib33","doi-asserted-by":"crossref","DOI":"10.1063\/1.3648118","article-title":"Log-normal distribution of single molecule fluorescence bursts in micro\/nano-fluidic channels","volume":"99","author":"Kish","year":"2011","journal-title":"Appl. Phys. Lett."},{"key":"10.1016\/j.jbc.2025.110913_bib34","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.abj8754","article-title":"Accurate prediction of protein structures and interactions using a three-track neural network","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.jbc.2025.110913_bib35","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1093\/bioinformatics\/btg362","article-title":"ModLoop: automated modeling of loops in protein structures","volume":"19","author":"Fiser","year":"2003","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jbc.2025.110913_bib36","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bpj.2009.04.013","article-title":"CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes","volume":"97","author":"Jo","year":"2009","journal-title":"Biophys. J."},{"key":"10.1016\/j.jbc.2025.110913_bib37","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD","volume":"26","author":"Phillips","year":"2005","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.jbc.2025.110913_bib38","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: an improved force field for folded and intrinsically disordered proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.jbc.2025.110913_bib39","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1021\/jp101759q","article-title":"Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types","volume":"114","author":"Klauda","year":"2010","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.jbc.2025.110913_bib40","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.jbc.2025.110913_bib41","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: a web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.jbc.2025.110913_bib42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: visual molecular dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph"},{"key":"10.1016\/j.jbc.2025.110913_bib43","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1021\/acs.jctc.1c01154","article-title":"Westpa 2.0: High-Performance upgrades for weighted ensemble simulations and analysis of longer-timescale applications","volume":"18","author":"Russo","year":"2022","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.jbc.2025.110913_bib44","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1021\/acs.jcim.3c01153","article-title":"AmberTools","volume":"63","author":"Case","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jbc.2025.110913_bib45","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.jbc.2025.110913_bib46","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1021\/acs.jpca.0c10724","article-title":"Adaptive binning scheme for weighted ensemble simulations","volume":"125","author":"Torrillo","year":"2021","journal-title":"J. Phys. Chem. A"},{"key":"10.1016\/j.jbc.2025.110913_bib47","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"10.1016\/j.jbc.2025.110913_bib48","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theor. Comput."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825027656?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925825027656?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:50:33Z","timestamp":1773838233000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925825027656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":48,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S0021925825027656"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2025.110913","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rewiring PTH receptor signaling: Hormone dimerization restores endosomal signaling lost in hypocalcemia-linked PTH mutant","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2025.110913","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology\u00e9","name":"copyright","label":"Copyright"}],"article-number":"110913"}}