PUBLICATION
Cardiovascular small heat shock protein HSPB7 is a kinetically-privileged RES sensor
- Authors
- Surya, S.L., Long, M.J.C., Urul, D.A., Zhao, Y., Mercer, E.J., Elsaid, I.M., Evans, T., Aye, Y.
- ID
- ZDB-PUB-180206-8
- Date
- 2018
- Source
- ACS Chemical Biology 13(7): 1824-1831 (Journal)
- Registered Authors
- Aye, Yimon, Evans, Todd
- Keywords
- none
- MeSH Terms
-
- Aldehydes/chemistry
- Aldehydes/metabolism*
- Alkylation
- Animals
- Cell Line, Tumor
- Cysteine/chemistry
- HEK293 Cells
- HSP27 Heat-Shock Proteins/chemistry
- HSP27 Heat-Shock Proteins/genetics
- HSP27 Heat-Shock Proteins/metabolism*
- Humans
- Kinetics
- Mutagenesis
- Protein Structure, Secondary
- Sequence Homology, Amino Acid
- Zebrafish
- PubMed
- 29397684 Full text @ ACS Chem. Biol.
Citation
Surya, S.L., Long, M.J.C., Urul, D.A., Zhao, Y., Mercer, E.J., Elsaid, I.M., Evans, T., Aye, Y. (2018) Cardiovascular small heat shock protein HSPB7 is a kinetically-privileged RES sensor. ACS Chemical Biology. 13(7):1824-1831.
Abstract
Small heat shock protein (sHSP)-B7 (HSPB7) is a muscle-specific member of the non-ATP-dependent sHSPs. The precise role of HSPB7 is enigmatic. Here we disclose that zebrafish Hspb7 is a kinetically-privileged sensor able to react rapidly with native reactive electrophilic signals (RES), when only sub-stoichiometric amounts of RES are available in proximity to Hspb7 expressed in living cells. Among the two Hspb7-cysteines, this RES-sensing is fulfilled by a single cysteine (C117). Purification and characterizations in vitro reveal that the rate for RES-adduction is among the most efficient reported for protein-cysteines with native carbonyl-based-RES. Covalent-ligand binding is accompanied by structural changes (increase in β-sheet-content) based on circular dichroism analysis. Among the two cysteines, only C117 is conserved across vertebrates; we show that the human ortholog is also capable of RES-sensing in cells. Furthermore, a cancer-relevant missense mutation reduces this RES-sensing property. This evolutionarily-conserved cysteine-biosensor may play a redox-regulatory role in cardioprotection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping