Alpha-helix 1 in the DNA-binding domain of heat shock factor 1 regulates its heat-induced trimerization and DNA-binding

Lü, Ming; Sohn, Kwang-Jea; Kim, Si-Won; Li, Chun-Ri; Kim, Suhkmann; Kim, Dong‐Kyoo; Park, Jang-Su

doi:10.1016/j.bbrc.2009.05.109

Cited by 7 publications

(9 citation statements)

References 24 publications

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“…In a previous study, trimerization in hHSF1 was found to occur via disulfide bond formation between the cysteine residues at positions 36 and 103. 19,22,23 Interestingly, the current study indicated that at least one cysteine is required for the trimerization of HSF1s regardless of its position (residue 36 or 103) and that trimerization can also occur via the formation of a different type of bond between cysteine and aromatic ring residues (tyrosine and phenylalanine).…”

Section: Introductionmentioning

confidence: 54%

“…Previous studies have shown that in hHSF1, cysteine residues at positions 36 and 103 form disulfide bonds at 42 °C. 19,22,23 In gHSF1 and wHSF1, while site 36 was occupied by cysteine, site 103 was occupied by tyrosine and phenylalanine, respectively. Considering that amino acids C, Y, and F at position 103 of these three HSF1 species affect the trimer formation temperature, the amino acids were mutated.…”

Section: Discussionmentioning

confidence: 99%

“…These two cysteines are located at the amino acid residue positions 36 and 103 (C36 and C103, respectively). 19,22,23 Additional research has shown that the proximity of aromatic amino acids such as phenylalanine (F) and tyrosine (Y) around residues 36 and 103 is required for the formation of a disulfide bridge between the two cysteines. 24 However, compared with hHSF1, little is known about the structure and formation of HSF1 and its trimerization in different species of fish.…”

Section: Introductionmentioning

confidence: 99%

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Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization

Lee,

Choi,

Kim

et al. 2024

Biochemistry

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In this study, we investigated the trimerization mechanism and structure of heat shock factor 1 (HSF1) using western blotting, tryptophan (Trp) fluorescence spectroscopy, and molecular modeling. First, we examined the DNA-binding domains of human (Homo sapiens), goldfish (Carassius auratus), and walleye pollock (Gadus chalcogrammus) HSF1s by mutating key residues (36 and 103) that are thought to directly affect trimer formation. Human, goldfish, and walleye pollock HSF1s contain cysteine at residue 36 but cysteine (C), tyrosine (Y), and phenylalanine (F), respectively, at residue 103. The optimal trimerization temperatures for the wild-type HSF1s of each species were found to be 42, 37, and 20 °C, respectively. Interestingly, a mutation experiment revealed that trimerization occurred at 42 °C when residue 103 was cysteine, at 37 °C when it was tyrosine, and at 20 °C when it was phenylalanine, regardless of the species. In addition, it was confirmed that when residue 103 of the three species was mutated to alanine, trimerization did not occur. This suggests that in addition to trimerization via disulfide bond formation between the cysteine residues in human HSF1, trimerization can also occur via the formation of a different type of bond between cysteine and aromatic ring residues such as tyrosine and phenylalanine. We also confirmed that at least one cysteine is required for the trimerization of HSF1s, regardless of its position (residue 36 or 103). Additionally, it was shown that the trimer formation temperature is related to growth and survival in fish.

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Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization

Lee,

Choi,

Kim

et al. 2024

Biochemistry

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“…The A20D mutation in the first helix of the DBD markedly inhibited HSF4b oligomerization. The first helix of the human HSF1 DBD is important for oligomerization and HSE-binding [34]. Interestingly, HSF4b-A20D was capable of binding to continuous HSE but not discontinuous HSEs.…”

Section: Discussionmentioning

confidence: 98%

DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts

Enoki

Mukoda²,

Furutani³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Heat shock transcription factor HSF4 is necessary for ocular lens development and fiber cell differentiation. Mutations of the human HSF4 gene have been implicated in congenital and age-related cataracts. Here, we show that HSF4 activates transcription of genes encoding crystallins and beaded filament structural proteins in lens epithelial cells. Five missense mutations that have been associated with congenital cataract inhibited DNA-binding of HSF4, which demonstrates the relationship between HSF4 mutations, loss of lens protein gene expression, and cataractogenesis. However, two missense mutations that have been associated with age-related cataract did not or only slightly alter HSF4 activity, implying that other genetic and environmental factors affect the functions of these mutant proteins.

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“…The DBD structure of Drosophila HSF suggests that an aromatic residue, Tyr92, had intramolecular interactions with the helix (H1) residues (Vuister et al, 1994). A previous study by Lu et al (2009a) reported that in human HSF1, Tyr60 can form intramolecular interactions with the first α-helix (H1), which exists in the DNA-binding domain (DBD) of HSF1. Two cysteine residues (C36 and C103) in HSF1 (hHSF1) participate in the formation of an intermolecular disulfide bond (SS bond), which is required for DNA binding (Lu et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

Functional HSF1 Requires Aromatic-Participant Interactions in Protecting Mouse Embryonic Fibroblasts against Apoptosis Via G2 Cell Cycle Arrest

Chang

Lü

Park

et al. 2012

Molecules and Cells

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The present study highlighted the aromatic-participant interactions in in vivo trimerization of HSF1 and got an insight into the process of HSF1 protecting against apoptosis. In mouse embryonic fibroblasts (MEFs), mutations of mouse HSF1 (W37A, Y60A and F104A) resulted in a loss of trimerization activity, impaired binding of the heat shock element (HSE) and lack of heat shock protein 70 (HSP70) expression after a heat shock. Under UV irradiation, wildtype mouse HSF1 protected the MEFs from UV-induced apoptosis, but none of the mutants offered protection. We found that normal expression of HSF1 was essential to the cell arrest in G2 phase, assisting with the cell cycle checkpoint. The cells that lack normal HSF1 failed to arrest in the G2 phase, resulting in the process of cell apoptosis. We conclude that the treatment with UV or heat shock stresses appears to induce the approach of HSF1 monomers directly via aromatic-participant interactions, followed by the formation of a HSF1 trimer. HSF1 protects the MEFs from the stresses through the expression of HSPs and a G2 cell cycle arrest.

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Alpha-helix 1 in the DNA-binding domain of heat shock factor 1 regulates its heat-induced trimerization and DNA-binding

Cited by 7 publications

References 24 publications

Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization

Intermolecular Interactions between Cysteine and Aromatic Amino Acids with a Phenyl Moiety in the DNA-Binding Domain of Heat Shock Factor 1 Regulate Thermal Stress-Induced Trimerization

DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts

Functional HSF1 Requires Aromatic-Participant Interactions in Protecting Mouse Embryonic Fibroblasts against Apoptosis Via G2 Cell Cycle Arrest

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