{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T14:31:00Z","timestamp":1767969060740,"version":"3.49.0"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010190","name":"Grand \u00c9quipement National De Calcul Intensif","doi-asserted-by":"publisher","award":["100567"],"award-info":[{"award-number":["100567"]}],"id":[{"id":"10.13039\/501100010190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNRS","award":["Institutional grant"],"award-info":[{"award-number":["Institutional grant"]}]},{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","award":["Institutional grant"],"award-info":[{"award-number":["Institutional grant"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Universit\u00e9 d'Angers","award":["Institutional grant"],"award-info":[{"award-number":["Institutional grant"]}]},{"name":"University of Carthage"},{"DOI":"10.13039\/501100008280","name":"Universite Angers","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008280","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>In vertebrates, the octopeptide angiotensin II (AngII) is an important <jats:italic>in vivo<\/jats:italic> regulator of the cardiovascular system. It acts mainly through two G protein-coupled receptors, AT1 and AT2. To better understand distinctive features of these receptors, we carried out a phylogenetic analysis that revealed a mirror evolution of AT1 and AT2, each one split into two clades, separating fish from terrestrial receptors. It also revealed that hallmark mutations occurred at, or near, the sodium binding site in both AT1 and AT2. Electrostatics computations and molecular dynamics simulations support maintained sodium binding to human AT1 with slow ingress from the extracellular side and an electrostatic component of the binding free energy around -3kT, to be compared to around -2kT for human AT2 and the \u03b4 opioid receptor. Comparison of the sodium binding modes in wild type and mutated AT1 and AT2 from humans and eels indicates that the allosteric control by sodium in both AT1 and AT2 evolved during the transition from fish to amniota. The unusual S7.46N mutation in AT1 is mirrored by a L3.36M mutation in AT2. In the presence of sodium, the N7.46 pattern in amniota AT1 stabilizes the inward orientation of N3.35 in the apo receptor, which should contribute to efficient N3.35 driven biased signaling. The M3.36 pattern in amniota AT2 favours the outward orientation of N3.35 and the receptor promiscuity. Both mutations have physiological consequences for the regulation of the renin-angiotensin system.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009732","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T18:33:01Z","timestamp":1645727581000},"page":"e1009732","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evolutionary information helps understand distinctive features of the angiotensin II receptors AT1 and AT2 in amniota"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3329-1831","authenticated-orcid":true,"given":"Rym","family":"Ben Boubaker","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-2062","authenticated-orcid":true,"given":"Asma","family":"Tiss","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-0285","authenticated-orcid":true,"given":"Daniel","family":"Henrion","sequence":"additional","affiliation":[]},{"given":"Hajer","family":"Guissouma","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-0987","authenticated-orcid":true,"given":"Marie","family":"Chabbert","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"issue":"10","key":"pcbi.1009732.ref001","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.cellsig.2014.06.011","article-title":"A century old renin-angiotensin system still grows with endless possibilities: AT1 receptor signaling cascades in cardiovascular physiopathology","volume":"26","author":"P Balakumar","year":"2014","journal-title":"Cellular signalling"},{"issue":"3","key":"pcbi.1009732.ref002","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1152\/physrev.00038.2017","article-title":"Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology","volume":"98","author":"SJ Forrester","year":"2018","journal-title":"Physiological reviews"},{"issue":"2","key":"pcbi.1009732.ref003","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41569-019-0244-8","article-title":"Counter-regulatory renin-angiotensin system in cardiovascular disease","volume":"17","author":"M Paz Ocaranza","year":"2020","journal-title":"Nature reviews Cardiology"},{"issue":"4","key":"pcbi.1009732.ref004","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1124\/pr.114.010454","article-title":"International Union of Basic and Clinical Pharmacology. 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