7wfw | pdb_00007wfw

sodium channel IV

spinqualitylabelsall models 7wfw, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7wfw is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CLR, LPE, NAG, P5S, PCW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [SCNAA_HUMAN] Congenital insensitivity to pain-anosmia-neuropathic arthropathy;Primary erythromelalgia;Sodium channelopathy-related small fiber neuropathy;Brugada syndrome;Paroxysmal extreme pain disorder;Romano-Ward syndrome. The disease is caused by variants affecting the gene represented in this entry. Function [SCNAA_HUMAN] Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms. Publication Abstract from PubMed The dorsal root ganglia-localized voltage-gated sodium (Nav) channel Nav1.8 represents a promising target for developing next-generation analgesics. A prominent characteristic of Nav1.8 is the requirement of more depolarized membrane potential for activation. Here we present the cryogenic electron microscopy structures of human Nav1.8 alone and bound to a selective pore blocker, A-803467, at overall resolutions of 2.7 to 3.2 A. The first voltage-sensing domain (VSDI) displays three different conformations. Structure-guided mutagenesis identified the extracellular interface between VSDI and the pore domain (PD) to be a determinant for the high-voltage dependence of activation. A-803467 was clearly resolved in the central cavity of the PD, clenching S6IV. Our structure-guided functional characterizations show that two nonligand binding residues, Thr397 on S6I and Gly1406 on S6III, allosterically modulate the channel's sensitivity to A-803467. Comparison of available structures of human Nav channels suggests the extracellular loop region to be a potential site for developing subtype-specific pore-blocking biologics. Structural basis for high-voltage activation and subtype-specific inhibition of human Nav1.8.,Huang X, Jin X, Huang G, Huang J, Wu T, Li Z, Chen J, Kong F, Pan X, Yan N Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208211119. doi:, 10.1073/pnas.2208211119. Epub 2022 Jul 19. PMID:35858452 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA