Heat shock factor

Function

Heat shock factor (HSF) are transcriptional activators of heat shock genes. HSF bind to heat shock sequence elements throughout the genome with a consensus array of three oppositely oriented sequence AGGAN and activate transcription. Each HSF monomer contains one C-terminal and 3 N-terminal leucine zippers. Two sequences flanking the N-terminal leucine zippers contain the consensus nuclear localization signal (NLS). The DNA-binding domain (DBD residues 193-281) of HSF lies in the N-terminal of the first NLS region^[1].

Relevance

Depletion of HSF-1 is associated with accumulation of pathogenic androgen receptor in neurodegenerative diseases^[2]. Increased expression of HSF-1 contributes to the reversal of cerebellar cell deficiency in rats carrying Alzheimer disease^[3].

Structural highlights

The DBD region of HSF shows ^[4]. Water molecules shown as red spheres.

3D structures of heat shock factor

Updated on 07-August-2025

2ldu – hHSF-1 DBD residues 193-281 – human - NMR

5hdg – hHSF-1 DBD
5d5u, 5d5v, 5hdn, 7dcj, 7dcs, 7dct – hHSF-1 DBD + DNA
5hdk – hHSF-2 DBD
5d8k, 5d8l, 7dci, 7dcu – hHSF-2 DBD + DNA
6j6v – hHSF-4 DBD
6j6w – hHSF-4 DBD (mutant)
8zys – hHSF-5 DBD + DNA
1fbu, 2hts – KlHSF DBD – Kluyveromyces lactis 1fbq, 1fbs, 3htf – KlHSF DBD (mutant) 3hsf - KlHSF DBD (mutant) – NMR
3hts – KlHSF DBD + DNA
1fyk, 1fyl, 1fym – KlHSF DBD (mutant) + DNA
1hks, 1hkt – HSF DBD – Drosophila melanogaster – NMR

References

1. ↑ Sarge KD, Murphy SP, Morimoto RI. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol. 1993 Mar;13(3):1392-407. PMID:8441385
2. ↑ Kondo N, Katsuno M, Adachi H, Minamiyama M, Doi H, Matsumoto S, Miyazaki Y, Iida M, Tohnai G, Nakatsuji H, Ishigaki S, Fujioka Y, Watanabe H, Tanaka F, Nakai A, Sobue G. Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration. Nat Commun. 2013;4:1405. doi: 10.1038/ncomms2417. PMID:23360996 doi:http://dx.doi.org/10.1038/ncomms2417
3. ↑ Jiang YQ, Wang XL, Cao XH, Ye ZY, Li L, Cai WQ. Increased heat shock transcription factor 1 in the cerebellum reverses the deficiency of Purkinje cells in Alzheimer's disease. Brain Res. 2013 Jun 26;1519:105-11. doi: 10.1016/j.brainres.2013.04.059. Epub, 2013 May 9. PMID:23665061 doi:http://dx.doi.org/10.1016/j.brainres.2013.04.059
4. ↑ Littlefield O, Nelson HC. A new use for the 'wing' of the 'winged' helix-turn-helix motif in the HSF-DNA cocrystal. Nat Struct Biol. 1999 May;6(5):464-70. PMID:10331875 doi:10.1038/8269