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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Jaeger AM, Pemble CW, Sistonen L, Thiele DJ
Förläggare: NATURE PUBLISHING GROUP
Publiceringsår: 2016
Tidskrift: Nature Structural and Molecular Biology
Tidskriftsakronym: NAT STRUCT MOL BIOL
Volym: 23
Nummer: 2
Artikelns första sida, sidnummer: 147
Artikelns sista sida, sidnummer: 154
Antal sidor: 10
ISSN: 1545-9993
eISSN: 1545-9985


Abstrakt

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.

Senast uppdaterad 2019-19-09 vid 05:31