pH Dependence of HSF1 trimerization is shaped by intramolecular interactions

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• Heat shock factor 1 (HSF1) is crucial for cellular stress responses.
• Previous research indicates low physiological pH activates HSF1 in vitro, but mechanisms are unclear.

Purpose of the Study:

• To elucidate the molecular mechanism of HSF1 activation by pH.
• To investigate the role of HSF1 trimerization in response to pH changes.

Main Methods:

• Extensive mutagenesis of human and goldfish HSF1.
• Analysis of HSF1 trimerization at varying pH levels.
• Investigating residue 103's role in HSF1 oligomerization.

Main Results:

• HSF1 trimerization pH optimum is determined by residue 103.
• Tyrosine at residue 103 significantly increases the optimal pH for trimerization.
• Protonation states of His101 and His110, influenced by residue 103, regulate HSF1 trimerization via interactions with Cys36.

Conclusions:

• Residue 103 is a key determinant of HSF1 pH-dependent trimerization.
• Histidine protonation state regulates intramolecular interactions, altering HSF1 oligomerization.
• This mechanism provides insight into HSF1's role in cellular pH homeostasis and stress response.