Structure of human lymphoid-specific helicase HELLS in its autoinhibitory state.

ABSTRACT: Helicase, Lymphoid Specific (HELLS), also known as Lymphoid-Specific Helicase (LSH), is a member of the SNF2 chromatin-remodeling family that regulates DNA methylation and heterochromatin organization. Unlike most chromatin remodelers, HELLS is catalytically inactive in its apo form and requires the DNA-binding protein CDCA7 for activation, though the underlying mechanism has remained unclear. Here, we combine biochemical, biophysical and cryo-electron microscopy analyses to define the structural basis of HELLS autoinhibition. HELLS alone assembles into a hexameric (trimer of dimers) architecture stabilized by interactions between its N-terminal coiled-coil (CC) domain and ATPase Lobe-1, while ATPase Lobe-2 remains flexible and disengaged. The CC domain functions both as an oligomerization

SUBMITTER: Kaur G 

PROVIDER: S-EPMC12885070 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature