ABCMdb

ABCC8 p.Lys205Glu

Predicted by SNAP2:	A: N (72%), C: N (57%), D: N (78%), E: N (82%), F: D (53%), G: N (66%), H: N (87%), I: N (57%), L: N (57%), M: N (57%), N: N (93%), P: N (82%), Q: N (82%), R: N (87%), S: N (87%), T: N (78%), V: N (57%), W: D (53%), Y: N (53%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: D, H: N, I: D, L: D, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D,

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Publications
[hide] Engineered interaction between SUR1 and Kir6.2 tha... J Gen Physiol. 2012 Aug;140(2):175-87. doi: 10.1085/jgp.201210803. Epub 2012 Jul 16. Pratt EB, Zhou Q, Gay JW, Shyng SL
Engineered interaction between SUR1 and Kir6.2 that enhances ATP sensitivity in KATP channels.
J Gen Physiol. 2012 Aug;140(2):175-87. doi: 10.1085/jgp.201210803. Epub 2012 Jul 16., [PMID:22802363]

Abstract [show]
The ATP-sensitive potassium (K(ATP)) channel consisting of the inward rectifier Kir6.2 and SUR1 (sulfonylurea receptor 1) couples cell metabolism to membrane excitability and regulates insulin secretion. Inhibition by intracellular ATP is a hallmark feature of the channel. ATP sensitivity is conferred by Kir6.2 but enhanced by SUR1. The mechanism by which SUR1 increases channel ATP sensitivity is not understood. In this study, we report molecular interactions between SUR1 and Kir6.2 that markedly alter channel ATP sensitivity. Channels bearing an E203K mutation in SUR1 and a Q52E in Kir6.2 exhibit ATP sensitivity approximately 100-fold higher than wild-type channels. Cross-linking of E203C in SUR1 and Q52C in Kir6.2 locks the channel in a closed state and is reversible by reducing agents, demonstrating close proximity of the two residues. Our results reveal that ATP sensitivity in K(ATP) channels is a dynamic parameter dictated by interactions between SUR1 and Kir6.2.

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Sentences [show]
No. Sentence Comment
102 Error bars represent SEM, and some are smaller than the symbols. (K199E, R202E, E203K, and K205E) and then coexpressed with WT-, Q52E-, or Q52R-Kir6.2. Login to comment
104 When coexpressed with WTKir6.2, only K205E-SUR1 had an obvious effect on ATP sensitivity, causing reduced inhibition by ATP (hereinafter "//" is used to denote heteromeric Kir6.2 and SUR1 combinations and "/" is used to separate multiple mutations in a single SUR1 or Kir6.2 subunit). Login to comment
107 Combination of K205E-SUR1 and Q52E-Kir6.2 yielded channels with decreased ATP sensitivity close to that seen in WT-Kir6//K205E-SUR1 channels. Login to comment
117 Only 1 mM ATP was tested in the cases of E203K-SUR1// Q52R-Kir6.2 and K205E-SUR1// Q52R-Kir6.2 because of extremely low ATP sensitivity. Login to comment