Abstract
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 α-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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Acknowledgements
This work was supported by NIH grant 1R01 EY017370 to REK. AFC is supported in part by NIH MBTG T32 GM008268 and the Hurd Fellowship in Biophysics from the UW School of Medicine.
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Clouser, A.F., Klevit, R.E. pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1. Cell Stress and Chaperones 22, 569–575 (2017). https://doi.org/10.1007/s12192-017-0783-z
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DOI: https://doi.org/10.1007/s12192-017-0783-z