Molecular consequences of SCA5 mutations in the spectrin-repeat domains of β-III-spectrin.

ABSTRACT: Spinocerebellar ataxia type 5 (SCA5) mutations in the protein β-III-spectrin cluster to the N-terminal actin-binding domain (ABD) and the central spectrin-repeat domains (SRDs). We previously reported that a common molecular consequence of ABD-localized SCA5 mutations is increased actin binding. However, little is known about the molecular consequences of the SRD-localized mutations. It is known that the SRDs of β-spectrin proteins interact with α-spectrin to form an α/β-spectrin dimer. In addition, it is known that SRDs neighboring the β-spectrin ABD enhance actin binding. Here, we tested the impact of the SRD-localized R480W and E532_M544del mutations on the binding of β-III-spectrin to α-II-spectrin and actin. R480W is associated with a severe infantile onset form of SCA5, while E532_M5

SUBMITTER: Denha SA 

PROVIDER: S-EPMC12269838 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature