Structural Effects of Disease-Related Mutations in Actin-Binding Period 3 of Tropomyosin.

ABSTRACT: Tropomyosin (Tpm) is an actin-binding coiled-coil protein. In muscle, it regulates contractions in a troponin/Ca²⁺-dependent manner and controls the thin filament lengths at the pointed end. Due to its size and periodic structure, it is difficult to observe small local structural changes in the coiled coil caused by disease-related mutations. In this study, we designed 97-residue peptides, Tpm1.1_64-154 and Tpm3.12_65-155, focusing on the actin-binding period 3 of two muscle isoforms. Using these peptides, we evaluated the effects of cardiomyopathy mutations: I92T and V95A in Tpm1.1, and congenital myopathy mutations R91P and R91C in Tpm3.12. We introduced a cysteine at the N-terminus of each fragment to promote the formation of the coiled-coil structure by d

SUBMITTER: Kuruba B 

PROVIDER: S-EPMC8622905 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature