Format

Send to

Choose Destination
Nat Struct Mol Biol. 2016 Feb;23(2):147-54. doi: 10.1038/nsmb.3150. Epub 2016 Jan 4.

Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA.
2
Duke University Human Vaccine Institute Macromolecular Crystallography Center, Duke University School of Medicine, Durham, North Carolina, USA.
3
Department of Biosciences, Åbo Akademi University, Turku, Finland.
4
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
5
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.

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.

PMID:
26727490
PMCID:
PMC4973471
DOI:
10.1038/nsmb.3150
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center