Calcium-dependent cooperativity and stability of Titin's tandem I82-I83 domains.

ABSTRACT: The muscle protein titin spans half a sarcomere, from M-line to Z-disk, 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-terminus 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 mdm-mouse model, which contains an 83-amino acid deletion spanning the C-terminus of the I83 domain and the N-terminus of the PEVK region, leading to muscular dystrophy with myositis. This mdm-deletion 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 th

SUBMITTER: Kelly CM 

PROVIDER: S-EPMC12611880 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature