{'fraction_non_alphanumeric': 0.018729641693811076, 'fraction_numerical': 0.004885993485342019, 'mean_word_length': 5.302564102564102, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Novel insights into the allosteric gating mechanism of MthK channel


 Allostery is a fundamental element during channel gating in response to an appropriate stimulus, by which events occurring at one site are transmitted to distal sites to regulate activity. To address how binding of the first Ca2+ ion at one of the eight chemically identical subunits facilitates the other Ca2+-binding events in MthK, a Ca2+-gated K+ channel containing a conserved ligand-binding RCK domain, we analyzed a large collection of MthK structures, and performed the corresponding thermodynamic and electrophysiological measurements. These structural and functional studies lead us to conclude that the conformations of the Ca2+-binding sites alternate between two quaternary states and exhibit significant differences in Ca2+ affinity. We further propose an allosteric model of MthK gating mechanism, by which a cascade of structural events connect the initial Ca2+-binding to the final changes of the ring structure that open the ion conduction pore. This mechanical model reveals the exquisite design that achieves the allosteric gating and could be of general relevance for the action of other ligand-gated ion channels containing RCK domain.