biostudies-literatureGaston BChildren’s Lung FoundationNIDA NIH HHSNHLBI NIH HHSEli Lilly FoundationHarrington Discovery InstituteNational Institutes of HealthNIH HHSOtherRiley Children’s Foundation134174https://www.ebi.ac.uk/biostudies/studies/S-EPMC7526540biostudies-literatureUnknown5(18)S-nitroso-l-cysteine (L-CSNO) behaves as a ligand. Its soluble guanylate cyclase-independent (sGC-independent) effects are stereoselective - that is, not recapitulated by S-nitroso-d-cysteine (D-CSNO) - and are inhibited by chemical congeners. However, candidate L-CSNO receptors have not been identified. Here, we have used 2 complementary affinity chromatography assays - followed by unbiased proteomic analysis - to identify voltage-gated K+ channel (Kv) proteins as binding partners for L-CSNO. Stereoselective L-CSNO-Kv interaction was confirmed structurally and functionally using surface plasmon resonance spectroscopy; hydrogen deuterium exchange; and, in Kv1.1/Kv1.2/Kvβ2-overexpressing cells, patch clamp assays. Remarkably, these sGC-independent L-CSNO effects did not involve S-nitrosylatJCI insightVoltage-gated potassium channel proteins and stereoselective S-nitroso-l-cysteine signaling.PMC7526540INCITEU01 DA051373P01HL101871EndowmentP01 HL128192Riley Children’s FoundationP01HL128192T32 HL125245T32HL125245S10 OD026882Harrington Discovery InstituteP01 HL101871SIG RR016789Getsy PBates JNWintrobe PStrassmaier TMarozkina NSmith LLewis TSeckler JKunze DLewis SJBurton STMorozkina TSKiselar JMcGee KBosch JHodges CAGaston BfalseVoltage-gated potassium channel proteins and stereoselective S-nitroso-l-cysteine signaling.S-nitroso-l-cysteine (L-CSNO) behaves as a ligand. Its soluble guanylate cyclase-independent (sGC-independent) effects are stereoselective - that is, not recapitulated by S-nitroso-d-cysteine (D-CSNO) - and are inhibited by chemical congeners. However, candidate L-CSNO receptors have not been identified. Here, we have used 2 complementary affinity chromatography assays - followed by unbiased proteomic analysis - to identify voltage-gated K+ channel (Kv) proteins as binding partners for L-CSNO. Stereoselective L-CSNO-Kv interaction was confirmed structurally and functionally using surface plasmon resonance spectroscopy; hydrogen deuterium exchange; and, in Kv1.1/Kv1.2/Kvβ2-overexpressing cells, patch clamp assays. Remarkably, these sGC-independent L-CSNO effects did not involve S-nitrosylat2020-01-01T00:00:00Z2020 Sep2026-04-17T11:08:50.633Z2025-06-01T03:53:55.164ZS-EPMC75265403279064510.1172/jci.insight.134174