Unmasking features of the auto-epitope essential for β₁ -adrenoceptor activation by autoantibodies in chronic heart failure.

ABSTRACT:

Aims

Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β₁ -adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine-map the conformational epitope within the second extracellular loop of the human β₁ -adrenoceptor (β₁ EC_II ) that is targeted by stimulating β₁ -receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto-epitope.

Methods a

SUBMITTER: Wolfel A 

PROVIDER: S-EPMC7373925 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature