9z04 | pdb_00009z04

Structure of human lymphoid-specific helicase HELLS in its auto-inhibitory state

spinqualitylabelsall models 9z04, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9z04 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.99Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease HELLS_HUMAN ICF syndrome. The disease may be caused by variants affecting the gene represented in this entry. Function HELLS_HUMAN ATP-dependent chromatin remodeler that regulates chromatin accessibility, DNA methylation, and histone modifications. It facilitates de novo DNA methylation at repetitive sequences and promotes transcriptional silencing via recruitment of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), contributing to heterochromatin formation and repression of transposable elements (PubMed:30307408). Also involved in DNA repair by recruiting DNA damage response mediators to double-strand breaks in heterochromatin, promoting homologous recombination via RBBP8/CtIP-dependent end resection (PubMed:22946062, PubMed:31802118). During meiosis, it is recruited by PRDM9 to recombination hotspots, aiding chromatin opening (PubMed:32001511). Through these diverse roles, is crucial for processes such as development, differentiation, and genomic stability (PubMed:22946062, PubMed:31802118). Involved in regulation of the expansion or survival of lymphoid cells (By similarity).[UniProtKB:Q60848] Publication Abstract from PubMed 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 scaffold and as an autoinhibitory module that restricts catalytic activity. Binding of CDCA7 and DNA promotes formation of an active HELLS-CDCA7-DNA ternary complex. CDCA7 recognizes hemimethylated CpG dinucleotides in both B-form and non-B-form DNA and stimulates HELLS ATPase activity. Together, these findings reveal the mechanism of HELLS autoinhibition and its activation by CDCA7 and DNA, providing new insight into how the HELLS-CDCA7-DNA ternary complex maintains DNA methylation and heterochromatin integrity. Structure of human lymphoid-specific helicase HELLS in its autoinhibited state.,Kaur G, Ren R, Lee J, Horton JR, Zhang X, Gao Y, Chen T, Cheng X Nucleic Acids Res. 2026 Mar 19;54(6):gkag326. doi: 10.1093/nar/gkag326. PMID:41954988 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA