Journal: Proceedings of the National Academy of Sciences of the United States of America
Article Title: Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death
Figure Lengend Snippet: Structure and stability of Hm1a. ( A ) Primary structures of Hm1a and Hm1b. Nonconserved residues are highlighted in blue. The disulfide-bond architecture is illustrated above the sequences. ( B ) 3D structure of Hm1a. Disulfide bonds are shown in red, β strands are green, and the N- and C-termini are labeled. ( C ) Cystine knot motif in Hm1a. The C15–C28 disulfide bond (orange) bisects a closed loop formed by the other two disulfide bonds (red) and the intervening sections of peptide backbone (gray). ( D ) Surface representation of Hm1a showing exposed hydrophobic residues that are conserved in Hm1b (green) and residues that differ between Hm1a and Hm1b (blue). ( E ) Speculative model for interaction of the hydrophobic face of Hm1a with the DIV voltage sensor of Na V 1.1. ( F ) Stability of Hm1a, hANP, and ziconotide in human CSF.
Article Snippet: The supernatant (10 μL) was then processed [150 mm × 2.1 mm; flow rate 0.2 mL/min; gradient of 2–40% solvent B (90% acetonitrile, 0.1% FA) in solvent A (0.1% FA) over 14 min] coupled to a TripleTOF 5600 mass spectrometer (AB SCIEX) with a cycle time of 0.2751 s. Peak areas were measured for triple-, quadruple-, and quintuple-charge states and were analyzed using PeakView and MultiQuant (Sciex) software. hANP (1 μM; GenScript) and ziconotide (ω-conotoxin MVIIA, 1 μM; Alomone Labs) served as controls.