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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jaeger, AM; Pemble, CW; Sistonen, L; Thiele, DJ

Published Date

  • February 2016

Published In

Volume / Issue

  • 23 / 2

Start / End Page

  • 147 - 154

PubMed ID

  • 26727490

Pubmed Central ID

  • 26727490

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.3150

Language

  • eng