SNAP output for PDB entry 5d8l [SNAP web server]

PDB-id

5d8l; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

X-ray (2.069 Å)

Summary

Human hsf2 DNA binding domain in complex with 3-site hse DNA at 2.1 angstroms resolution

Reference

Jaeger AM, Pemble CW, Sistonen L, Thiele DJ (2016): "Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors." Nat.Struct.Mol.Biol., 23, 147-154. doi: 10.1038/nsmb.3150.

Abstract

Heat-shock transcription factor (HSF) family members function in stress protection and in human diseases including proteopathies, neurodegeneration and cancer. The mechanisms that drive distinct post-translational modifications, cofactor recruitment and target-gene activation for specific HSF paralogs are unknown. We present crystal structures of the human HSF2 DNA-binding domain (DBD) bound to DNA, revealing an unprecedented view of HSFs that provides insights into their unique biology. The HSF2 DBD structures resolve a new C-terminal helix that directs wrapping of the coiled-coil domain around DNA, thereby exposing paralog-specific sequences of the DBD surface for differential post-translational modifications and cofactor interactions. We further demonstrate a direct interaction between HSF1 and HSF2 through their coiled-coil domains. Together, these features provide a new model for HSF structure as the basis for differential and combinatorial regulation, which influences the transcriptional response to cellular stress.