{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:26Z","timestamp":1790614226198,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"name":"New Zealand Lotteries Commission"},{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001516","name":"National Heart Foundation of New Zealand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001516","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wellcome Trust","award":["091496"],"award-info":[{"award-number":["091496"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Receptor activity\u2010modifying proteins (\n RAMP<\/jats:styled-content>\n s) define the pharmacology of the calcitonin receptor\u2010like receptor (\n CLR<\/jats:styled-content>\n ). The interactions of the different\n RAMP<\/jats:styled-content>\n s with this class\n B GPCR<\/jats:styled-content>\n yield high\u2010affinity calcitonin gene\u2010related peptide (\n CGRP<\/jats:styled-content>\n ) or adrenomedullin (\n AM<\/jats:styled-content>\n ) receptors. However, the mechanism for this is unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Guided by receptor models, we mutated residues in the\n N<\/jats:styled-content>\n \u2010terminal helix of\n CLR<\/jats:styled-content>\n ,\n RAMP2<\/jats:styled-content>\n and\n RAMP3<\/jats:styled-content>\n hypothesized to be involved in peptide interactions. These were assayed for\n cAMP<\/jats:styled-content>\n production with\n AM<\/jats:styled-content>\n ,\n AM2<\/jats:styled-content>\n and\n CGRP<\/jats:styled-content>\n together with their cell surface expression. Binding studies were also conducted for selected mutants.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n An important domain for peptide interactions on\n CLR<\/jats:styled-content>\n from\n I32<\/jats:styled-content>\n to\n I52<\/jats:styled-content>\n was defined. Although\n I41<\/jats:styled-content>\n was universally important for binding and receptor function, the role of other residues depended on both ligand and\n RAMP<\/jats:styled-content>\n . Peptide binding to\n CLR<\/jats:styled-content>\n \/\n RAMP3<\/jats:styled-content>\n involved a more restricted range of residues than that to\n CLR<\/jats:styled-content>\n \/\n RAMP1<\/jats:styled-content>\n or\n CLR<\/jats:styled-content>\n \/\n RAMP2<\/jats:styled-content>\n .\n E101<\/jats:styled-content>\n of\n RAMP2<\/jats:styled-content>\n had a major role in\n AM<\/jats:styled-content>\n interactions, and\n F111<\/jats:styled-content>\n \/\n W84<\/jats:styled-content>\n of\n RAMP2<\/jats:styled-content>\n \/3 was important with each peptide.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n RAMP<\/jats:styled-content>\n \u2010dependent effects of\n CLR<\/jats:styled-content>\n mutations suggest that the different\n RAMP<\/jats:styled-content>\n s control accessibility of peptides to binding residues situated on the\n CLR N<\/jats:styled-content>\n \u2010terminus.\n RAMP3<\/jats:styled-content>\n appears to alter the role of specific residues at the\n CLR\u2010RAMP<\/jats:styled-content>\n interface compared with\n RAMP1<\/jats:styled-content>\n and\n RAMP2<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12508","type":"journal-article","created":{"date-parts":[[2013,11,6]],"date-time":"2013-11-06T23:46:48Z","timestamp":1383781608000},"page":"772-788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Receptor activity\u2010modifying protein\u2010dependent effects of mutations in the calcitonin receptor\u2010like receptor: implications for adrenomedullin and calcitonin gene\u2010related peptide pharmacology"],"prefix":"10.1111","volume":"171","author":[{"given":"H A","family":"Watkins","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C S","family":"Walker","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K N","family":"Ly","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"Bailey","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Barwell","sequence":"additional","affiliation":[{"name":"School of Life Sciences Aston University Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D R","family":"Poyner","sequence":"additional","affiliation":[{"name":"School of Life Sciences Aston University Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D L","family":"Hay","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland Auckland New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011907328682"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.05.007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.11.014"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707246"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2009.10.021"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01525.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.67.1.20"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm276"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)74020-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33302"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.06.039"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.03.027"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.05.014"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027953"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.06.015"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.21.2.138"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(05)03370-2"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12357"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01530.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33022"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2003"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.221"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20660"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/30666"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.11.076"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2377"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.02.131"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.186072"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706404104"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2009.02.004"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801027105"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805749200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.022905"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg522"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.2.233"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00541.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.047142"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2011.03.004"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02197.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305332200"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708740200"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1626"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12393"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.06.026"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)01368-1"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.033829"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12072"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12118"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12508","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12508","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.12508","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:08:29Z","timestamp":1694131709000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,13]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1111\/bph.12508"],"URL":"https:\/\/doi.org\/10.1111\/bph.12508","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,13]]},"assertion":[{"value":"2013-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-10-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}