Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2.

ABSTRACT: While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing c

SUBMITTER: Goradia N 

PROVIDER: S-EPMC11187106 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature