Saponaro, Andrea ; Cantini, Francesca ; Porro, Alessandro ; Bucchi, Annalisa ; DiFrancesco, Dario ; Maione, Vincenzo ; Donadoni, Chiara ; Introini, Bianca ; Mesirca, Pietro ; Mangoni, Matteo Elia ; Thiel, Gerhard ; Banci, Lucia ; Santoro, Bina ; Moroni, Anna (2018)
A synthetic peptide that prevents cAMP regulation in mammalian Hyperpolarization-activated Cyclic Nucleotide-regulated (HCN) channels.
In: eLife, 7
Article, Bibliographie
This is the latest version of this item.
Abstract
Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian 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 (TRIP8b) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (human hHCN1, mHCn2, rbHCN4) and in the cardiac current I in rabbit and mouse sinoatrial node cardiomyocytes. Guided by a NMR-derived structural model that identifies the key molecular interactions between TRIP8b and HCN CNBD, we further designed a cell-penetrating peptide (TAT-TRIP8b) which successfully prevented b-adrenergic activation of mouse I leaving the stimulation of the L-type calcium current (I) unaffected. TRIP8b represents a novel approach to selectively control HCN activation, which yields the promise of a more targeted pharmacology compared to pore blockers.
| Item Type: | Article |
|---|---|
| Erschienen: | 2018 |
| Creators: | Saponaro, Andrea ; Cantini, Francesca ; Porro, Alessandro ; Bucchi, Annalisa ; DiFrancesco, Dario ; Maione, Vincenzo ; Donadoni, Chiara ; Introini, Bianca ; Mesirca, Pietro ; Mangoni, Matteo Elia ; Thiel, Gerhard ; Banci, Lucia ; Santoro, Bina ; Moroni, Anna |
| Type of entry: | Bibliographie |
| Title: | A synthetic peptide that prevents cAMP regulation in mammalian Hyperpolarization-activated Cyclic Nucleotide-regulated (HCN) channels. |
| Language: | English |
| Date: | 20 June 2018 |
| Journal or Publication Title: | eLife |
| Volume of the journal: | 7 |
| Corresponding Links: | |
| Abstract: | Binding of TRIP8b to the cyclic nucleotide binding domain (CNBD) of mammalian 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 (TRIP8b) that recapitulates affinity and gating effects of TRIP8b in HCN isoforms (human hHCN1, mHCn2, rbHCN4) and in the cardiac current I in rabbit and mouse sinoatrial node cardiomyocytes. Guided by a NMR-derived structural model that identifies the key molecular interactions between TRIP8b and HCN CNBD, we further designed a cell-penetrating peptide (TAT-TRIP8b) which successfully prevented b-adrenergic activation of mouse I leaving the stimulation of the L-type calcium current (I) unaffected. TRIP8b represents a novel approach to selectively control HCN activation, which yields the promise of a more targeted pharmacology compared to pore blockers. |
| Identification Number: | pmid:29923826 |
| Divisions: | 10 Department of Biology 10 Department of Biology > Plant Membrane Biophyscis (20.12.23 renamed in Biology of Algae and Protozoa) |
| Date Deposited: | 26 Jun 2018 08:42 |
| Last Modified: | 03 Jul 2024 02:30 |
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| Suche nach Titel in: | TUfind oder in Google |
Available Versions of this Item
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A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. (deposited 01 Mar 2022 08:53)
- A synthetic peptide that prevents cAMP regulation in mammalian Hyperpolarization-activated Cyclic Nucleotide-regulated (HCN) channels. (deposited 26 Jun 2018 08:42) [Currently Displayed]
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