Polyazine nanoparticles as anchors of PQQ glucose dehydrogenase for its most efficient bioelectrocatalysis.

We report on the drop-cast production of glucose biosensors based on the most efficient bioelectrocatalysis by pyrroloquinoline quinone dependent glucose dehydrogenase (PQQ GDH). To orient the enzyme upon immobilization we suggest using poly(Methylene Green) (p(MG)) nanoparticles acting as anchors. Synthesis of polymeric anchors has been carried out in course of Methylene Green electropolymerization, which allowed to tune polymer-to-monomer ratio in the drop-cast mixtures varying the monomer concentration and applying different number of potential sweep cycles.

Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation.

Titin is the largest protein found in nature and spans half a sarcomere in vertebrate striated muscle. The protein has multiple functions, including in the organisation of the thick filament and acting as a molecular spring during the muscle contraction cycle. Missense variants in titin have been linked to both cardiac and skeletal myopathies.

Obscurin Rho GEF domains are phosphorylated by MST-family kinases but do not exhibit nucleotide exchange factor activity towards Rho GTPases in vitro.

Obscurin is a giant muscle protein (>800 kDa) featuring multiple signalling domains, including an SH3-DH-PH domain triplet from the Trio-subfamily of guanosine nucleotide exchange factors (GEFs). While previous research suggests that these domains can activate the small GTPases RhoA and RhoQ in cells, in vitro characterization of these interactions using biophysical techniques has been hampered by the intrinsic instability of obscurin GEF domains. To study substrate specificity, mechanism and regulation of obscurin GEF function by individual domains, we successfully optimized recombinant production of obscurin GEF domains and found that MST-family kinases phosphorylate the obscurin DH domain at Thr5798.

Synergy between Membrane Currents Prevents Severe Bradycardia in Mouse Sinoatrial Node Tissue.

Bradycardia is initiated by the sinoatrial node (SAN), which is regulated by a coupled-clock system. Due to the clock coupling, reduction in the 'funny' current (I), which affects SAN automaticity, can be compensated, thus preventing severe bradycardia. We hypothesize that this fail-safe system is an inherent feature of SAN pacemaker cells and is driven by synergy between I and other ion channels.

Molecular noise filtering in the β-adrenergic signaling network by phospholamban pentamers.

Phospholamban (PLN) is an important regulator of cardiac calcium handling due to its ability to inhibit the calcium ATPase SERCA. β-Adrenergic stimulation reverses SERCA inhibition via PLN phosphorylation and facilitates fast calcium reuptake. PLN also forms pentamers whose physiological significance has remained elusive.