Saponaro, Andrea ; Cantini, Francesca ; Porro, Alessandro ; Bucchi, Annalisa ; DiFrancesco, Dario ; Maione, Vincenzo ; Donadoni, Chiara ; Introini, Bianca ; Mesirca, Pietro ; Mangoni, Matteo E. ; Thiel, Gerhard ; Banci, Lucia ; Santoro, Bina ; Moroni, Anna (2022):
A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. (Publisher's Version)
In: eLife, 2018, eLife Sciences Publications, ISSN 2050-084X,
DOI: 10.26083/tuprints-00013339,
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Item Type: | Article |
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Origin: | Secondary publication |
Status: | Publisher's Version |
Title: | A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels |
Language: | English |
Abstract: | Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels prevents their regulation by cAMP. Since TRIP8b is expressed exclusively in the brain, we envisage that it can be used for orthogonal control of HCN channels beyond the central nervous system. To this end, we have identified by rational design a 40-aa long peptide (TRIP8bnano) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (hHCN1, mHCN2, rbHCN4) and in the cardiac current If in rabbit and mouse sinoatrial node cardiomyocytes. Guided by an NMR-derived structural model that identifies the key molecular interactions between TRIP8bnano and the HCN CNBD, we further designed a cell-penetrating peptide (TAT-TRIP8bnano) which successfully prevented β-adrenergic activation of mouse If leaving the stimulation of the L-type calcium current (ICaL) unaffected. TRIP8bnano represents a novel approach to selectively control HCN activation, which yields the promise of a more targeted pharmacology compared to pore blockers. |
Journal or Publication Title: | eLife |
Volume of the journal: | 2018 |
Place of Publication: | Darmstadt |
Publisher: | eLife Sciences Publications |
Collation: | 22 Seiten |
Classification DDC: | 500 Naturwissenschaften und Mathematik > 580 Pflanzen (Botanik) 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
Divisions: | 10 Department of Biology > Plant Membrane Biophysics |
Date Deposited: | 01 Mar 2022 08:53 |
Last Modified: | 02 Mar 2023 07:39 |
DOI: | 10.26083/tuprints-00013339 |
Corresponding Links: | |
URN: | urn:nbn:de:tuda-tuprints-133393 |
URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/13339 |
PPN: | 505396238 |
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