非天然或错误折叠的蛋白在细胞应激下的积累被认为是从伴侣调节蛋白中释放单体HSF1 (Guo Y et al. 2001)。释放的HSF1单体迅速转化为同型三聚体(Baler R et al. 1993;Herbomel G et al . 2013)。三聚化后，HSF1会发生显著的构象变化，导致稳定的三股α -螺旋螺旋结构与单个单体单元的氨基端疏水结构域组装(Rabindran SK et al. 1993;左俊等1994,1995;nef DW et al. 2013)。生化和结构分析强烈表明，单体到三聚体的转变在几个相互依赖的水平上受到紧密调控。因此，HSPs和辅助因子结合HSF1单体可以防止三聚体(Zou J et al.1998;郭勇等，2001)。此外，三聚结构域(LZ1-LZ3)中的亮氨酸拉链(LZ)被认为通过与HSF1羧基端LZ4的分子内螺旋相互作用，使HSF1保持非活性单体形式。 while LZ interactions between trimerization domains of individual monomeric units facilitate homotrimerization (Rabindran SK et al. 1993; Zuo J et al. 1994, 1995; Neef DW et al. 2013). HSF1 flexible linker region between DNA binding domain and first LZ of the trimerization domain was also found to modulate the monomer-trimer equilibrium (Liu PCC and Thiele DJ 1999). Furthermore, intermolecular disulfide bonds between cysteine residues 36 and 103 were reported to stabilize HSF1 trimer, while intramolecular disulfide crosslink inhibited HSF1 oligomerization (Lu M et al. 2008, 2009). Moreover, redox regulatory mechanisms were shown to regulate thiol-disulfide exchange and the conformation and activity of mammalian HSF1 in response to stress (Manalo DJ et al. 2002; Ahn SG and Thiele DJ 2003).

一个包含翻译延伸因子EEF1A1 (eEF1A)和一个长链非编码RNA HSR1(热休克RNA-1)的核蛋白复合物被证明介导HSF1的三聚体(Shamovsky I et al. 2006)。