{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:34:33Z","timestamp":1793468073739,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2038,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ES0901"],"award-info":[{"award-number":["01ES0901"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010571","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft, Forschung und Technologie","doi-asserted-by":"publisher","award":["0315363"],"award-info":[{"award-number":["0315363"]}],"id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ES0901"],"award-info":[{"award-number":["01ES0901"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010571","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft, Forschung und Technologie","doi-asserted-by":"publisher","award":["0315363"],"award-info":[{"award-number":["0315363"]}],"id":[{"id":"10.13039\/501100010571","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and\/or second extracellular loops of cardiac \u03b21-adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine-map the conformational epitope within the second extracellular loop of the human \u03b21-adrenoceptor (\u03b21ECII) that is targeted by stimulating \u03b21-receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto-epitope.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Non-conserved amino acids within the \u03b21ECII loop (compared with the amino acids constituting the ECII loop of the \u03b22-adrenoceptor) were one by one replaced with alanine; potential intra-loop disulfide bridges were probed by cysteine\u2013serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking \u03b21ECII \u00b1 the above replacements, and (ii) by (auto)antibody stimulation of human \u03b21-adrenoceptors bearing corresponding point mutations. With the use of stimulating \u03b21-receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the \u03b21ECII loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK211\u2013214 motif and (ii) the intra-loop disulfide bond C209\u2194C215. Of note, aberrant intra-loop disulfide bond C209\u2194C216 almost fully disrupted the functional auto-epitope in cyclopeptides.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The conformational auto-epitope targeted by cardio-pathogenic \u03b21-receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the \u03b21ECII loop bearing the NDPK211\u2013214 motif and the C209\u2194C215 bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in \u03b21-autoantibody-positive CHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12747","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T06:49:43Z","timestamp":1590043783000},"page":"1830-1841","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Unmasking Features of the Auto-Epitope Essential for \u03b21-Adrenoceptor Activation by Autoantibodies in Chronic Heart Failure"],"prefix":"10.1093","volume":"7","author":[{"given":"Angela","family":"W\u00f6lfel","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Rudolf-Virchow-Centre , Josef-Schneider-Str. 2, 97080, W\u00fcrzburg ,","place":["Germany"]},{"name":"Rudolf-Virchow-Centre, Pierre Fabre Dermo-Kosmetik GmbH , Jechtinger Stra\u00dfe 13, 79111, Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"S\u00e4ttele","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Zechmeister","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Interdisciplinary Bank of Biomaterials and Data (ibdw), University Hospital of W\u00fcrzburg , Straubm\u00fchlweg 2A, D-97078, W\u00fcrzburg ,","place":["Germany"]},{"name":"Comprehensive Heart Failure Centre (CFHC) , Am Schwarzenberg 11, 978078, W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav O.","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Institute for Molecular Cardiology, Department of Cardiology and Pneumology, University Hospital Hamburg-Eppendorf , Martinistra\u00dfe 52, 20246, Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Lohse","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Rudolf-Virchow-Centre , Josef-Schneider-Str. 2, 97080, W\u00fcrzburg ,","place":["Germany"]},{"name":"Institute Max Delbr\u00fcck Center for Molecular Research , Berlin-Buch, Robert-Koch-Str. 40, 1000, Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Boege","sequence":"additional","affiliation":[{"name":"Rudolf-Virchow-Centre, Institute of Clinical Chemistry and Laboratory Diagnostics, University Hospital , Moorenstra\u00dfe 5, 40225, D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Jahns*","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Interdisciplinary Bank of Biomaterials and Data (ibdw), University Hospital of W\u00fcrzburg , Straubm\u00fchlweg 2A, D-97078, W\u00fcrzburg ,","place":["Germany"]},{"name":"Comprehensive Heart Failure Centre (CFHC) , Am Schwarzenberg 11, 978078, W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Boivin-Jahns","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, University of W\u00fcrzburg , Versbacher Str. 9, D-97078, Wuerzburg ,","place":["Germany"]},{"name":"Comprehensive Heart Failure Centre (CFHC) , Am Schwarzenberg 11, 978078, W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"2026012115040063100_ehf212747-bib-0001","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1161\/CIR.0000000000000366","article-title":"Executive summary: heart disease and stroke statistics\u20142016 update: a report from the American Heart 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