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Cardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.

TitleCardiovascular Small Heat Shock Protein HSPB7 Is a Kinetically Privileged Reactive Electrophilic Species (RES) Sensor.
Publication TypeJournal Article
Year of Publication2018
AuthorsSurya, SL, Long, MJC, Urul, DA, Zhao, Y, Mercer, EJ, EIsaid, IM, Evans, T, Aye, Y
JournalACS Chem Biol
Volume13
Issue7
Pagination1824-1831
Date Published2018 Jul 20
ISSN1554-8937
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 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.

DOI10.1021/acschembio.7b00925
Alternate JournalACS Chem. Biol.
PubMed ID29397684
PubMed Central IDPMC6260788
Grant ListDP2 GM114850 / GM / NIGMS NIH HHS / United States
R35 HL135778 / HL / NHLBI NIH HHS / United States
S10 RR025502 / RR / NCRR NIH HHS / United States