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PLN interacts with sarco\/endoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -ATPase (SERCA) and regulates calcium uptake, which is modulated by the protein kinase A (PKA)-dependent phosphorylation of PLN during the fight-or-flight response. Here, we present the crystal structures of the catalytic domain of mouse PKA in complex with wild-type and DCM-mutant PLNs. Our structures, combined with the results from other biophysical and biochemical assays, reveal a common disease mechanism: the mutations in PLN reduce its phosphorylation level by changing its conformation and weakening its interactions with PKA. In addition, we demonstrate that another more ubiquitous SERCA-regulatory peptide, called another-regulin (ALN), shares a similar mechanism mediated by PKA in regulating SERCA activity.\n                  <\/jats:p>","DOI":"10.7554\/elife.75346","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T09:00:16Z","timestamp":1647507616000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.75346","source":"Crossref","is-referenced-by-count":21,"title":["Structures of PKA\u2013phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-3988","authenticated-orcid":true,"given":"Juan","family":"Qin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/012tb2g32","id-type":"ROR","asserted-by":"publisher"}],"name":"Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency; Collaborative Innovation Center of Chemical Science and Engineering; 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