5D8L

Human HSF2 DNA Binding Domain in complex with 3-site HSE DNA at 2.1 Angstroms Resolution

Summary for 5D8L

• Entry DOI: 10.2210/pdb5d8l/pdb
• Related: 5D8K
• Descriptor: DNA (5'-D(P*GP*TP*GP*AP*AP*TP*AP*TP*TP*CP*TP*AP*GP*AP*AP*CP*C)-3'), Heat shock factor protein 2, DNA (5'-D(*GP*GP*TP*TP*CP*TP*AP*GP*AP*AP*TP*AP*TP*TP*CP*AP*C)-3'), ... (4 entities in total)
• Functional Keywords: transcription factor, dna, hsf, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q03933
• Total number of polymer chains: 8
• Total formula weight: 73023.02

Authors

Jaeger, A.M.,Pemble, C.W.,Thiele, D.J. (deposition date: 2015-08-17, release date: 2016-01-06, Last modification date: 2024-03-06)

Primary citation

Jaeger, A.M.,Pemble, C.W.,Sistonen, L.,Thiele, D.J.
Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors.
Nat.Struct.Mol.Biol., 23:147-154, 2016

PubMed 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.

PubMed: 26727490
DOI: 10.1038/nsmb.3150

Experimental method

X-RAY DIFFRACTION (2.069 Å)