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

Publication ,  Journal Article
Jaeger, AM; Pemble, CW; Sistonen, L; Thiele, DJ
Published in: Nature structural & molecular biology
February 2016

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.

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Published In

Nature structural & molecular biology

DOI

EISSN

1545-9985

ISSN

1545-9993

Publication Date

February 2016

Volume

23

Issue

2

Start / End Page

147 / 154

Related Subject Headings

  • Transcription Factors
  • Sumoylation
  • Protein Interaction Domains and Motifs
  • Protein Conformation
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Developmental Biology
 

Citation

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Jaeger, A. M., Pemble, C. W., Sistonen, L., & Thiele, D. J. (2016). Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors. Nature Structural & Molecular Biology, 23(2), 147–154. https://doi.org/10.1038/nsmb.3150
Jaeger, Alex M., Charles W. Pemble, Lea Sistonen, and Dennis J. Thiele. “Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors.Nature Structural & Molecular Biology 23, no. 2 (February 2016): 147–54. https://doi.org/10.1038/nsmb.3150.
Jaeger AM, Pemble CW, Sistonen L, Thiele DJ. Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors. Nature structural & molecular biology. 2016 Feb;23(2):147–54.
Jaeger, Alex M., et al. “Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors.Nature Structural & Molecular Biology, vol. 23, no. 2, Feb. 2016, pp. 147–54. Epmc, doi:10.1038/nsmb.3150.
Jaeger AM, Pemble CW, Sistonen L, Thiele DJ. Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors. Nature structural & molecular biology. 2016 Feb;23(2):147–154.

Published In

Nature structural & molecular biology

DOI

EISSN

1545-9985

ISSN

1545-9993

Publication Date

February 2016

Volume

23

Issue

2

Start / End Page

147 / 154

Related Subject Headings

  • Transcription Factors
  • Sumoylation
  • Protein Interaction Domains and Motifs
  • Protein Conformation
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Developmental Biology