期刊
CELL STRESS & CHAPERONES
卷 22, 期 4, 页码 569-575出版社
SPRINGER
DOI: 10.1007/s12192-017-0783-z
关键词
Heat shock protein; Acidosis; Nuclear magnetic resonance (NMR); alpha-crystallin domain (ACD); Oligomeric structure; Structural regulation; HSPB1; Hsp27
类别
资金
- NIH [1R01 EY017370]
- NIH MBTG [T32 GM008268]
- Hurd Fellowship in Biophysics from the UW School of Medicine
The holdase activity and oligomeric propensity of human small heat shock proteins (sHSPs) are regulated by environmental factors. However, atomic-level details are lacking for the mechanisms by which stressors alter sHSP responses. We previously demonstrated that regulation of HSPB5 is mediated by a single conserved histidine over a physiologically relevant pH range of 6.5-7.5. Here, we demonstrate that HSPB1 responds to pH via a similar mechanism through pH-dependent structural changes that are induced via protonation of the structurally analogous histidine. Results presented here show that acquisition of a positive charge, either by protonation of His124 or its substitution by lysine, reduces the stability of the dimer interface of the alpha-crystallin domain, increases oligomeric size, and modestly increases chaperone activity. Our results suggest a conserved mechanism of pH-dependent structural regulation among the human sHSPs that possess the conserved histidine, although the functional consequences of the structural modulations vary for different sHSPs.
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