2MPF

Solution structure human HCN2 CNBD in the cAMP-unbound state

2MPF の概要

• エントリーDOI: 10.2210/pdb2mpf/pdb
• NMR情報: BMRB: 19977
• 分子名称: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (1 entity in total)
• 機能のキーワード: hcn channels, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : Q9UL51
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17987.89

構造登録者

Saponaro, A.,Pauleta, S.R.,Cantini, F.,Matzapetakis, M.,Hammann, C.,Banci, L.,Thiel, G.,Santoro, B.,Moroni, A. (登録日: 2014-05-16, 公開日: 2014-09-03, 最終更新日: 2024-05-15)

主引用文献

Saponaro, A.,Pauleta, S.R.,Cantini, F.,Matzapetakis, M.,Hammann, C.,Donadoni, C.,Hu, L.,Thiel, G.,Banci, L.,Santoro, B.,Moroni, A.
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
Proc.Natl.Acad.Sci.USA, 111:14577-14582, 2014

PubMed 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.

PubMed: 25197093
DOI: 10.1073/pnas.1410389111

実験手法

SOLUTION NMR