ON THE COVER
Zn2+ (magenta sphere) binds to an extracellular (top) site that is readily accessible to water molecules (cyan spheres). Experimental data indicate that Zn2+ occupancy alters Hv1 gating via long-range conformational coupling to an intracellular Coulombic network. Protein backbone is represented by colored ribbons and selected ionizable side chains are shown in colored stick representation; F150 is white. For clarity, lipids are not shown. Snapshot is selected from the Hv1 F·Zn2+ c0 molecular dynamics trajectory (t = 130 ns).
See page 863.
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JGP 100th Anniversary
The Jans recollect features of the scientific environments that influenced their careers.
Cui reflects on new coarse-grained simulations demonstrating that mitochondrial ATP synthase dimers spontaneously self-associate.
Islas evaluates two papers that provide mechanistic insight into pH-dependent gating in HV1 proton channels.
MacDougall et al. review the structure and function of the calcium sensor synaptotagmin-7 in exocytosis.
Cardiomyopathy mutation (F88L) in troponin T abolishes length dependency of myofilament Ca2+ sensitivity
The F88L mutation in cardiac troponin T (TnTF88L) is associated with hypertrophic cardiomyopathy. Reda and Chandra reveal that it abolishes length-mediated increase in myofilament Ca2+ sensitivity and attenuates cooperative mechanisms governing length-dependent activation.
Ligand binding and activation properties of the purified bacterial cyclic nucleotide–gated channel SthK
SthK is a bacterial cyclic nucleotide–gated ion channel from Spirochaeta thermophila. By optimizing the expression and purification of SthK, Schmidpeter et al. show that cAMP and cGMP bind to the channel with similar affinity but activate it with different efficacy.
Voltage-gated proton currents were first discovered in snail neurons. Thomas et al. identify a snail proton channel gene that codes for a rapidly activating proton channel that differs from other proton channels, in particular by its low sensitivity to intracellular pH.
Voltage-gated proton channels open appropriately in myriad physiological situations because their gating is powerfully modulated by both pHo and pHi. Cherny et al. serendipitously identify a histidine at the inner end of the S3 helix that is required for the response to pHi.
Hv1 proteins form a voltage-gated proton channel that is inhibited by extracellular Zn2+. De La Rosa et al find that extracellular Zn2+ is octahedrally coordinated by specific protein atoms and that Zn2+ occupancy modulates voltage sensor activation in Hv1 by long-range conformational coupling to a conserved intracellular electrostatic network.
A-kinase anchoring proteins are required for β-adrenergic stimulation of L-type Ca2+ channels in cardiac myocytes, but the molecular species that is responsible for this regulation remains unknown. Yu et al. reveal that Cypher/Zasp is a key regulator of β-adrenergic regulation in cardiac myocytes.