{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:50:48Z","timestamp":1775886648286,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The muscle protein titin spans half a sarcomere, from M\u2010line to Z\u2010disk, and is essential for both active and passive stretch. The N2A region of titin plays a critical role in various regulatory processes through its binding interactions. Located at the C\u2010terminus of the N2A region, adjacent to the PEVK region, are the I82 and I83 domains, which are key to binding calpain\/p94. However, this interaction is absent in the\n                    <jats:italic>mdm<\/jats:italic>\n                    \u2010mouse model, which contains an 83\u2010amino acid deletion spanning the C\u2010terminus of the I83 domain and the N\u2010terminus of the PEVK region, leading to muscular dystrophy with myositis. This\n                    <jats:italic>mdm<\/jats:italic>\n                    \u2010deletion disrupts the structure of the I83 domain, preventing normal force enhancement in the presence of calcium and inhibiting eccentric contractions. Our lab has demonstrated that the I83 domain exhibits calcium sensitivity at concentrations similar to those found in active muscle. In this current study, we further demonstrate that the tandem I82\u2010I83 domains exhibit cooperative unfolding, as seen by a single unfolding event, and that calcium enhances the stability of the tandem I82\u2010I83 domains. The NMR structure of this construct exhibits a tighter interface between I82 and I83 than is observed in the crystal structure, suggesting that the two structures might represent the structure in the relaxed state versus the structure under force. The calcium response of these domains is hypothesized to affect the function of the N2A region during muscle activation.\n                  <\/jats:p>","DOI":"10.1002\/pro.70378","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T05:51:26Z","timestamp":1763013086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calcium\u2010dependent cooperativity and stability of Titin's tandem\n                    <scp>I82<\/scp>\n                    \u2010\n                    <scp>I83<\/scp>\n                    domains"],"prefix":"10.1002","volume":"34","author":[{"given":"Colleen M.","family":"Kelly","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Massachusetts Lowell  Lowell Massachusetts USA"},{"name":"UMass Movement Center University of Massachusetts Lowell  Lowell Massachusetts 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