Panel A shows a side view of two opposite H C N channel subunits highlighting key domains, with arrows indicating major directions of conformational changes across the structure and numbered positions marking regions associated with functional transitions. Panel B shows a side view of the channel illustrating collective displacement patterns, where arrows represent coordinated movements within the cytosolic region relative to the rest of the structure. Panel C shows a top view of the channel emphasizing rotational-like rearrangements of domains, with displacement vectors indicating the direction and relative organization of structural changes.
Implications of ENM/LRT analysis for cAMP-mediated gating of HCN channels. (A–C) Side view of two opposite subunits of HCN channel as in Fig 1. Selected arrows indicate main directions of conformational movements of critical domains throughout the protein following cAMP binding. The numbers suggest functional consequences of these movements for cAMP-mediated gating: (1) ligand binding in one monomer has positive and negative impacts on cooperative binding to remaining monomers; (2) the C-linker approaches S4; (3) rotational movement of the C-linker causes via HCND a tilting of the S4 domain; (4) tilting of S4 promotes opening of a gating canal for modulation of electrical field surrounding S4. (5) Opening of the inner gate is promoted. Side view (B) and top view (C) of image in A showing how cAMP binding promotes a right handed (A and B) or anticlockwise (C) rotation in the cytosolic domain (opaque) and how this is translated by the C-linker into a tilting movement of the transmembrane domains (full color) in the opposite direction. See caption Fig. 5 for the magnitude/lengths of the arrows.