Saponaro, Andrea ; Pauleta, Sofia R. ; Cantini, Francesca ; Matzapetakis, Manolis ; Hammann, Christian ; Donadoni, Chiara ; Hu, Lei ; Thiel, Gerhard ; Banci, Lucia ; Santoro, Bina ; Moroni, Anna (2014)
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
In: Proceedings of the National Academy of Sciences of the United States of America, 11 (40)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by interacting with the channel CNBD. To unravel the molecular mechanisms underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free form and mapped on it the TRIP8b interaction site. We reconstruct here the full conformational changes induced by cAMP binding to the HCN channel CNBD. Our results show that TRIP8b does not compete with cAMP for the same binding region; rather, it exerts its inhibitory action through an allosteric mechanism, preventing the cAMP-induced conformational changes in the HCN channel CNBD.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2014 |
| Autor(en): | Saponaro, Andrea ; Pauleta, Sofia R. ; Cantini, Francesca ; Matzapetakis, Manolis ; Hammann, Christian ; Donadoni, Chiara ; Hu, Lei ; Thiel, Gerhard ; Banci, Lucia ; Santoro, Bina ; Moroni, Anna |
| Art des Eintrags: | Bibliographie |
| Titel: | Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function. |
| Sprache: | Englisch |
| Publikationsjahr: | 2014 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Proceedings of the National Academy of Sciences of the United States of America |
| Jahrgang/Volume einer Zeitschrift: | 11 |
| (Heft-)Nummer: | 40 |
| Kurzbeschreibung (Abstract): | cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by interacting with the channel CNBD. To unravel the molecular mechanisms underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free form and mapped on it the TRIP8b interaction site. We reconstruct here the full conformational changes induced by cAMP binding to the HCN channel CNBD. Our results show that TRIP8b does not compete with cAMP for the same binding region; rather, it exerts its inhibitory action through an allosteric mechanism, preventing the cAMP-induced conformational changes in the HCN channel CNBD. |
| 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: | 16 Sep 2014 09:41 |
| Letzte Änderung: | 13 Nov 2014 07:59 |
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