Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor
| Autor: | Todd Evans, Marcus J. C. Long, Yi Zhao, Daniel A. Urul, Yimon Aye, Emily J. Mercer, Sanjna L. Surya, Islam M. EIsaid |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Circular dichroism Alkylation HSP27 Heat-Shock Proteins 010402 general chemistry 01 natural sciences Biochemistry Article Protein Structure Secondary 03 medical and health sciences Protein structure Cell Line Tumor Heat shock protein Animals Humans Cysteine Zebrafish chemistry.chemical_classification Aldehydes Sequence Homology Amino Acid biology Mutagenesis HEK 293 cells General Medicine biology.organism_classification 0104 chemical sciences Amino acid Kinetics HEK293 Cells 030104 developmental biology chemistry Biophysics Molecular Medicine |
| Zdroj: | ACS Chemical Biology. 13:1824-1831 |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.7b00925 |
| Popis: | 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 that is able to react rapidly with native reactive electrophilic species (RES), when only substoichiometric 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. |
| Databáze: | OpenAIRE |
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