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Cover Image
Cover Image
ON THE COVER
The crystal structure of the human KCNH2 channel (hKCNH2) cyclic nucleotide-binding homology domain (CNBHD), resolved at 1.5 Å resolution (blue mesh). The structure highlights a newly identified E807-R863 salt-bridge (dashed line) as a vital component of hKCNH2 channel function. Indeed, by its proximity to the canonical KCNH intrinsic ligand motif, consisting of the 860FNL862 tripeptide (yellow sticks), this salt-bridge may serve as a strategically positioned linchpin, supporting both the spatial organization of the intrinsic ligand and the intracellular complex interface. Image © Ben-Bassat et al., 2020. See http://doi.org/10.1085/jgp.20191250 - PDF Icon PDF LinkTable of Contents
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Editorial
Research News
The pre-M1 helix controls NMDA receptor gating
Researchers identify key residue in GluN2A subunit that may regulate channel opening by organizing a network of aromatic amino acids.
Commentary
Move quickly to detach: Strain rate–dependent myosin detachment and cardiac relaxation
Chung considers a new model that describes how a muscle responds to stretch and its implications on myosin detachment and physiology.
Research Articles
Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges
Palmer et al. demonstrate that a stretch-induced enhancement of the myosin crossbridge detachment rate is sufficient to explain the force response of cardiac muscle to a quick stretch and would benefit diastolic function in a beating heart.
The mechanisms shaping CA2 pyramidal neuron action potential bursting induced by muscarinic acetylcholine receptor activation
Robert et al. reveal that muscarinic receptor activation causes hippocampal CA2 pyramidal neurons to depolarize and fire bursts of action potentials. The properties of these bursts are regulated by synaptic inputs, as well as T-type calcium channels, D-type potassium channels, and SK channels.
NMDA receptor channel gating control by the pre-M1 helix
Mutations in the pre-M1 helix of NMDA receptor subunits are associated with neurological disease. McDaniel et al. reveal that the helix influences channel gating, potentially through interactions with a network of aromatic amino acids within the subunit’s pre-M1 and pore-forming M3 helices and the adjacent subunit’s M4 helix.
Communication
Structure of KCNH2 cyclic nucleotide-binding homology domain reveals a functionally vital salt-bridge
Human KCNH2 are key channels governing cardiac repolarization. Here, a 1.5 Å resolution structure of their cyclic nucleotide-binding homology domain is presented. Structural analysis and electrophysiological validation reveal a novel salt-bridge that plays an important role in hKCNH2 functional regulation.
