The HCN CNBD–TRIP8b_nano complex. (A) Ribbon representation of the NMR-based model structure of the complex between human HCN2 CNBD (light gray) and TRIP8b_nano (gold). The structural elements of both proteins involved in the binding are labeled as follows: for the CNBD, E′-helix (αE′) and A-helix (αA), which form, together with their inter-helical loop, the N-terminal helical bundle; C-helix (αC); for TRIP8b_nano, helix N (N) and helix C (C). Negatively charged residues of TRIP8b_nano and positively charged residues of CNBD (αC), which are involved in the electrostatic interaction, are shown as sticks, labeled and colored in red and blue, respectively. D252 of TRIP8b_nano and N547 of the N-bundle loop and are shown as sticks and labeled. (B) Ribbon representation of human HCN2 CNBD (dark gray) bound to cAMP (PDB accession no. 3U10). cAMP (green stick) is shown within its binding pocket composed by the β-roll and the distal region of α helix C, which acts as a lid and closes cAMP within the β-roll. Residue R662 (yellow stick) of α helix C, which contacts cAMP, is shown. The structural elements of CNBD are labeled.