Protein functional dynamics from the rigorous global analysis of DEER data: Conditions, components, and conformations
DEER spectroscopy can be used to investigate the conformational equilibria of proteins. In this tutorial, we illustrate the rigorous global analysis of DEER data to quantitively analyze these equilibria to determine the populations of distinct intermediates under varying biochemical conditions.
Activation of skeletal muscle involves unfolding of myosin motors from their OFF conformation in resting muscle. X-ray diffraction from muscles contracting at longer sarcomere length show that motor unfolding does not depend on the availability of local actin-binding sites.
The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation
Savalli et al. reveal the early molecular events preceding skeletal muscle contraction by optically tracking the conformational changes of each of the four CaV1.1 voltage-sensing domains, which govern the voltage-dependent activation of both CaV1.1 and RYR1 channels.
Known mutations in CaV1.1 in hypokalemic periodic paralysis (HypoPP) occur at arginine residues of the voltage sensor domain and cause an anomalous inward gating pore current. By studying several HypoPP mutations, Wu et al. show that the magnitude of these gating pore currents is mutation specific.
EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues
Thapa et al. present a method to label Kv2 potassium channels in live tissue using a variant of the tarantula toxin guangxitoxin-1E and to image them using two-photon microscopy. Their approach enables the inference of conformational changes in situ from changes in fluorescence intensity.
Synchrony of sarcomeric movement regulates left ventricular pump function in the in vivo beating mouse heart
Sarcomeric contraction in cardiomyocytes serves as the basis for the heart’s pump function. Kobirumaki-Shimozawa et al. show that sarcomere synchrony regulates myofibrillar dynamics and, accordingly, rhythmic myocyte contractions in the in vivo beating mouse heart.