Structural insights into assembly and function of the RSC chromatin remodeling complex

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• SWI/SNF chromatin remodelers are crucial for DNA accessibility and gene regulation.
• Dysregulation of these remodelers, including the Saccharomyces cerevisiae RSC complex, is implicated in various cancers.

Purpose of the Study:

• To elucidate the structural mechanisms governing the assembly and regulation of the RSC subcomplex.
• To understand the role of actin-related proteins (ARPs) in Sth1 conformation and function.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) to determine high-resolution structures.
• Biochemical assays to analyze protein interactions and functional consequences.

Main Results:

• ARP binding induces a helical conformation in the Sth1 helicase-SANT-associated (HSA) domain.
• The ARP module exhibits a significant rotation relative to the full RSC, highlighting conformational flexibility.
• A conserved interaction between Sth1 and the nucleosome acidic patch enhances chromatin remodeling activity.

Conclusions:

• Large conformational changes are integral to Sth1 regulation and RSC assembly.
• Understanding these mechanisms provides insights into how cancer-associated mutations in SWI/SNF remodelers contribute to disease.