Alessio Accardi

2 months ago | nature.com | Elizabeth Kim |Sangyun Lee |Alessio Accardi

AbstractBK channels are large-conductance calcium (Ca2+)-activated potassium channels crucial for neuronal excitability, muscle contraction, and neurotransmitter release. The pore-forming (α) subunits co-assemble with auxiliary (β and γ) subunits that modulate their function. Previous studies demonstrated that the N-termini of β2-subunits can inactivate BK channels, but with no structural correlate.

Jul 31, 2024 | nature.com | Elizabeth Kim |Xiaoan Wu |Sangyun Lee |Kevin Cunningham |Marta Perez |Peter Goldstein | +4 more

AbstractHyperpolarization-activated cyclic nucleotide-gated (HCN) channels1 are essential for pacemaking activity and neural signalling2,3. Drugs inhibiting HCN1 are promising candidates for management of neuropathic pain4 and epileptic seizures5. The general anaesthetic propofol (2,6-di-iso-propylphenol) is a known HCN1 allosteric inhibitor6 with unknown structural basis.

Apr 29, 2024 | nature.com | Zhang Feng |Alessio Accardi

AbstractActivation of Ca2+-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown.