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

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Jaeger AM, Pemble CW, Sistonen L, Thiele DJ
Publisher: NATURE PUBLISHING GROUP
Publication year: 2016
Journal: Nature Structural and Molecular Biology
Journal acronym: NAT STRUCT MOL BIOL
Volume number: 23
Issue number: 2
Start page: 147
End page: 154
Number of pages: 10
ISSN: 1545-9993
eISSN: 1545-9985


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.

Last updated on 2019-17-06 at 05:08