6q61

Pore-modulating toxins exploit inherent slow inactivation to block K+ channels

spinqualitylabelsall models 6q61, resolution 1.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6q61 is a 1 chain structure with sequence from Conus striatus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.3Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VKTS1_CONST Blocks specifically voltage-activated potassium channels (Kv) of the Shaker family (IC(50)=1.33 nM). Publication Abstract from PubMed Voltage-dependent potassium channels (K(v)s) gate in response to changes in electrical membrane potential by coupling a voltage-sensing module with a K(+)-selective pore. Animal toxins targeting K(v)s are classified as pore blockers, which physically plug the ion conduction pathway, or as gating modifiers, which disrupt voltage sensor movements. A third group of toxins blocks K(+) conduction by an unknown mechanism via binding to the channel turrets. Here, we show that Conkunitzin-S1 (Cs1), a peptide toxin isolated from cone snail venom, binds at the turrets of K(v)1.2 and targets a network of hydrogen bonds that govern water access to the peripheral cavities that surround the central pore. The resulting ectopic water flow triggers an asymmetric collapse of the pore by a process resembling that of inherent slow inactivation. Pore modulation by animal toxins exposes the peripheral cavity of K(+) channels as a novel pharmacological target and provides a rational framework for drug design. Pore-modulating toxins exploit inherent slow inactivation to block K(+) channels.,Karbat I, Altman-Gueta H, Fine S, Szanto T, Hamer-Rogotner S, Dym O, Frolow F, Gordon D, Panyi G, Gurevitz M, Reuveny E Proc Natl Acad Sci U S A. 2019 Sep 10;116(37):18700-18709. doi: , 10.1073/pnas.1908903116. Epub 2019 Aug 23. PMID:31444298 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA