6br0 | pdb_00006br0

Solution NMR structure for CcoTx-I

spinqualitylabelsall models 6br0 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6br0 is a 1 chain structure with sequence from Ceratogyrus marshalli. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Ligands: NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TX1_CERMR Publication Abstract from PubMed Gating modifier toxins (GMTs) are venom-derived peptides isolated from spiders and other venomous creatures that modulate activity of disease-relevant voltage-gated ion channels and are therefore being pursued as therapeutic leads. The amphipathic surface profile of GMTs has prompted the proposal that some GMTs simultaneously bind to the cell membrane and voltage-gated ion channels in a trimolecular complex. Here we examined whether there is a relationship among spider GMT amphipathicity, membrane binding and potency or selectivity for voltage-gated sodium (NaV) channels. We used NMR spectroscopy and in silico calculations to examine the structures and physicochemical properties of a panel of nine GMTs and deployed surface plasmon resonance to measure GMT affinity for lipids putatively found in proximity to NaV channels. Electrophysiology was used to quantify GMT activity on NaV1.7, an ion channel linked to chronic pain. Selectivity of the peptides was further examined against a panel of NaV channel subtypes. We show that GMTs adsorb to the outer leaflet of anionic lipid bilayers through electrostatic interactions. We did not observe a direct correlation between GMT amphipathicity and affinity for lipid bilayers. Furthermore, GMT-lipid bilayer interactions did not correlate with potency or selectivity for NaVs. We therefore propose that increased membrane binding is unlikely to improve subtype selectivity and that the conserved amphipathic GMT surface profile is an adaptation that facilitates simultaneous modulation of multiple NaVs. Gating modifier toxins isolated from spider venom: modulation of voltage-gated sodium channels and the role of lipid membranes.,Agwa AJ, Peigneur S, Chow CY, Lawrence N, Craik DJ, Tytgat J, King GF, Henriques ST, Schroeder CI J Biol Chem. 2018 Apr 27. pii: RA118.002553. doi: 10.1074/jbc.RA118.002553. PMID:29703751 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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