Structural analysis of X-linked retinoschisis mutations reveals distinct classes which differentially effect retinoschisin function.

ABSTRACT: Retinoschisin, an octameric retinal-specific protein, is essential for retinal architecture with mutations causing X-linked retinoschisis (XLRS), a monogenic form of macular degeneration. Most XLRS-associated mutations cause intracellular retention, however a subset are secreted as octamers and the cause of their pathology is ill-defined. Therefore, here we investigated the solution structure of the retinoschisin monomer and the impact of two XLRS-causing mutants using a combinatorial approach of biophysics and cryo-EM. The retinoschisin monomer has an elongated structure which persists in the octameric assembly. Retinoschisin forms a dimer of octamers with each octameric ring adopting a planar propeller structure. Comparison of the octamer with the hexadecamer structure indicated little c

SUBMITTER: Ramsay EP 

PROVIDER: S-EPMC5418834 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature