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

AM Jaeger, CW Pemble, Lea Sistonen, DJ Thiele

Tutkimustuotos: LehtiartikkeliArtikkelivertaisarvioitu

44 Sitaatiot (Scopus)

Abstrakti

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.
AlkuperäiskieliEi tiedossa
Sivut147–154
Sivumäärä10
JulkaisuNature Structural and Molecular Biology
Vuosikerta23
Numero2
DOI - pysyväislinkit
TilaJulkaistu - 2016
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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