Saponaro, Andrea ; Thiel, Gerhard ; Moroni, Anna (2021)
Structural and functional approaches to studying cAMP regulation of HCN channels.
In: Biochemical Society transactions
doi: 10.1042/BST20210290
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are primarily activated by voltage and further modulated by cAMP. While cAMP binding alone does not open the channel, its presence facilitates the action of voltage, increasing channel open probability. Functional results indicate that the membrane-based voltage sensor domain (VSD) communicates with the cytosolic cyclic nucleotide-binding domain (CNBD), and vice-versa. Yet, a mechanistic explanation on how this could occur in structural terms is still lacking. In this review, we will discuss the recent advancement in understanding the molecular mechanisms connecting the VSD with the CNBD in the tetrameric organization of HCN channels unveiled by the 3D structures of HCN1 and HCN4. Data show that the HCN domain transmits cAMP signal to the VSD by bridging the cytosolic to the membrane domains. Furthermore, a metal ion coordination site connects the C-linker to the S4-S5 linker in HCN4, further facilitating cAMP signal transmission to the VSD in this isoform.
Typ des Eintrags: | Artikel |
---|---|
Erschienen: | 2021 |
Autor(en): | Saponaro, Andrea ; Thiel, Gerhard ; Moroni, Anna |
Art des Eintrags: | Bibliographie |
Titel: | Structural and functional approaches to studying cAMP regulation of HCN channels |
Sprache: | Englisch |
Publikationsjahr: | 23 November 2021 |
Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Biochemical Society transactions |
DOI: | 10.1042/BST20210290 |
Kurzbeschreibung (Abstract): | Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are primarily activated by voltage and further modulated by cAMP. While cAMP binding alone does not open the channel, its presence facilitates the action of voltage, increasing channel open probability. Functional results indicate that the membrane-based voltage sensor domain (VSD) communicates with the cytosolic cyclic nucleotide-binding domain (CNBD), and vice-versa. Yet, a mechanistic explanation on how this could occur in structural terms is still lacking. In this review, we will discuss the recent advancement in understanding the molecular mechanisms connecting the VSD with the CNBD in the tetrameric organization of HCN channels unveiled by the 3D structures of HCN1 and HCN4. Data show that the HCN domain transmits cAMP signal to the VSD by bridging the cytosolic to the membrane domains. Furthermore, a metal ion coordination site connects the C-linker to the S4-S5 linker in HCN4, further facilitating cAMP signal transmission to the VSD in this isoform. |
ID-Nummer: | pmid:34812892 |
Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen) |
Hinterlegungsdatum: | 30 Nov 2021 06:21 |
Letzte Änderung: | 30 Nov 2021 06:21 |
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