ABCC1 p.Lys1322Asp
| Predicted by SNAP2: | A: D (75%), C: D (71%), D: D (91%), E: D (85%), F: D (80%), G: D (80%), H: D (66%), I: D (75%), L: D (75%), M: D (66%), N: D (71%), P: D (91%), Q: D (75%), R: D (53%), S: D (71%), T: D (66%), V: D (75%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Sulfonylurea receptors regulate the channel pore i... Biochem J. 2014 Dec 15;464(3):343-54. doi: 10.1042/BJ20140273. Lodwick D, Rainbow RD, Rubaiy HN, Al Johi M, Vuister GW, Norman RI
Sulfonylurea receptors regulate the channel pore in ATP-sensitive potassium channels via an intersubunit salt bridge.
Biochem J. 2014 Dec 15;464(3):343-54. doi: 10.1042/BJ20140273., [PMID:25236767]
Abstract [show]
ATP-sensitive potassium channels play key roles in many tissues by coupling metabolic status to membrane potential. In contrast with other potassium channels, the pore-forming Kir6 subunits must co-assemble in hetero-octameric complexes with ATP-binding cassette (ABC) family sulfonylurea receptor (SUR) subunits to facilitate cell surface expression. Binding of nucleotides and drugs to SUR regulates channel gating but how these responses are communicated within the complex has remained elusive to date. We have now identified an electrostatic interaction, forming part of a functional interface between the cytoplasmic nucleotide-binding domain-2 of SUR2 subunits and the distal C-terminus of Kir6 polypeptides that determines channel response to nucleotide, potassium channel opener and antagonist. Mutation of participating residues disrupted physical interaction and regulation of expressed channels, properties that were restored in paired charge-swap mutants. Equivalent interactions were identified in Kir6.1- and Kir6.2-containing channels suggesting a conserved mechanism of allosteric regulation.
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No. Sentence Comment
90 Single charge reversals in both full-length Kir6.2 and MBP-SUR2-(1294-1358) restored co-immunoprecipitation to at least WT levels from mixtures of Kir6.2-K338E-SUR2- E1318R, Kir6.2-D323K-SUR2-K1322D and Kir6.2-D323K- SUR2-Q1336E (Figures 5e and 5f), indicating that all three of the proposed electrostatic interactions may be important structurally and/or for assembly.
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ABCC1 p.Lys1322Asp 25236767:90:192
status: NEW