| Structural highlights
Function
HSF1_HUMAN DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to "two-site" head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures.
Structures of heat shock factor trimers bound to DNA.,Feng N, Feng H, Wang S, Punekar AS, Ladenstein R, Wang DC, Zhang Q, Ding J, Liu W iScience. 2021 Aug 5;24(9):102951. doi: 10.1016/j.isci.2021.102951. eCollection , 2021 Sep 24. PMID:34458700[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
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- ↑ Knauf U, Newton EM, Kyriakis J, Kingston RE. Repression of human heat shock factor 1 activity at control temperature by phosphorylation. Genes Dev. 1996 Nov 1;10(21):2782-93. PMID:8946918
- ↑ Kline MP, Morimoto RI. Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol. 1997 Apr;17(4):2107-15. PMID:9121459
- ↑ Xia W, Guo Y, Vilaboa N, Zuo J, Voellmy R. Transcriptional activation of heat shock factor HSF1 probed by phosphopeptide analysis of factor 32P-labeled in vivo. J Biol Chem. 1998 Apr 10;273(15):8749-55. PMID:9535852
- ↑ Guo Y, Guettouche T, Fenna M, Boellmann F, Pratt WB, Toft DO, Smith DF, Voellmy R. Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex. J Biol Chem. 2001 Dec 7;276(49):45791-9. Epub 2001 Oct 2. PMID:11583998 doi:https://dx.doi.org/10.1074/jbc.M105931200
- ↑ Soncin F, Zhang X, Chu B, Wang X, Asea A, Ann Stevenson M, Sacks DB, Calderwood SK. Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2. Biochem Biophys Res Commun. 2003 Apr 4;303(2):700-6. PMID:12659875
- ↑ Hietakangas V, Ahlskog JK, Jakobsson AM, Hellesuo M, Sahlberg NM, Holmberg CI, Mikhailov A, Palvimo JJ, Pirkkala L, Sistonen L. Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Mol Cell Biol. 2003 Apr;23(8):2953-68. PMID:12665592
- ↑ Wang X, Khaleque MA, Zhao MJ, Zhong R, Gaestel M, Calderwood SK. Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding. J Biol Chem. 2006 Jan 13;281(2):782-91. Epub 2005 Nov 8. PMID:16278218 doi:M505822200
- ↑ Feng N, Feng H, Wang S, Punekar AS, Ladenstein R, Wang DC, Zhang Q, Ding J, Liu W. Structures of heat shock factor trimers bound to DNA. iScience. 2021 Aug 5;24(9):102951. PMID:34458700 doi:10.1016/j.isci.2021.102951
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