Issues
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ON THE COVER
Mock screen of low (grey) versus high (red) Ca2+ on fluorescence lifetime in IANBD-cTnCT53C exchanged myofibrils: average lifetimes (dashes) and 3× S.D. (lines). Insets: IANBD-TnCT53C (orange-green); fluorescence microscopy of IANBD-cTnCT53C (green) and α-actinin (yellow) in myofibril; Ca2+ effect on fluorescence waveforms in myofibrils (zoom-in of lifetime decays); and thin filament cartoon. Image © Dvornikov et al., 2022. See https://doi.org/10.1085/jgp.202113054. - PDF Icon PDF LinkTable of Contents
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Research News
Steady-state measurement of charge-voltage curves
A new gating current recording protocol shows that gating hysteresis is a kinetic phenomenon, rather than an inherent thermodynamic property of Shaker potassium channels.
Commentary
A loosely coordinated interaction site for arachidonic acid on ASICs
Molecular dynamics simulations reveal a putative interaction surface for PUFAs on TM1 of ASICs that is not tightly conserved between isoforms.
Reviews
Role of ryanodine receptor 2 and FK506-binding protein 12.6 dissociation in pulmonary hypertension
ROS-dependent dissociation of FKBP12.6 mediates pulmonary artery vasoconstriction and pulmonary hypertension.
Viewpoint
Mechanosensitive membrane proteins: Usual and unusual suspects in mediating mechanotransduction
This Viewpoint uncovers the phylogenetic, structural, and functional diversity of membrane mechanosensors, recent successes, and the on-going challenges for studying them in reconstituted systems and intact cells, tissues, plants, and animals.
Articles
Multiscale molecular dynamics simulations predict arachidonic acid binding sites in human ASIC1a and ASIC3 transmembrane domains
Ananchenko and Musgaard use multiscale MD simulations to predict an outer leaflet PUFA-binding region on the ASIC protein transmembrane domain, building on existing functional data, and further supporting direct interactions of PUFAs with ASICs.
Cooperativity of myosin II motors in the non-regulated and regulated thin filaments investigated with high-speed AFM
The activation status of thin filaments determines cooperativity between neighboring myosin heads in muscle.
Conformational changes linked to ADP release from human cardiac myosin bound to actin-tropomyosin
Cryo-EM was used to elucidate high-resolution structures of actin-tropomyosin filaments decorated with human cardiac myosin in the rigor and ADP-bound states. Differences in the myosin lever arm orientation correlate with the overall actomyosin-linked force-sensitivity.
Fluorescence lifetime-based assay reports structural changes in cardiac muscle mediated by effectors of contractile regulation
Dvornikov et al. test a new high-throughput fluorescence lifetime-based assay using a human cardiac troponin C probe in cardiac myofibrils. The assay sensitivity and precision allow for the detection of key structural changes in cTnC that reports changes in thick and filament proteins in health and disease, which promises to have utility in screening therapeutic compounds that target these proteins.
Sarcomere length affects Ca2+ sensitivity of contraction in ischemic but not non-ischemic myocardium
Isometric force–pCa relationships were measured in human myocardial strips at 37°C. Ca2+ sensitivity increased with sarcomere length in samples from donors and patients with ischemic heart failure. Ca2+ sensitivity did not change with length in samples from patients with non-ischemic heart failure.
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