ABCC1 p.Phe1295Ile
| Predicted by SNAP2: | A: D (63%), C: D (53%), D: D (85%), E: D (80%), G: D (80%), H: D (71%), I: N (57%), K: D (80%), L: N (53%), M: N (57%), N: D (71%), P: D (85%), Q: D (75%), R: D (80%), S: D (71%), T: D (71%), V: D (59%), W: D (71%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, G: D, H: D, I: D, K: 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] Kir6.2 activation by sulfonylurea receptors: a dif... Physiol Rep. 2015 Sep;3(9). pii: e12533. doi: 10.14814/phy2.12533. Principalli MA, Dupuis JP, Moreau CJ, Vivaudou M, Revilloud J
Kir6.2 activation by sulfonylurea receptors: a different mechanism of action for SUR1 and SUR2A subunits via the same residues.
Physiol Rep. 2015 Sep;3(9). pii: e12533. doi: 10.14814/phy2.12533., [PMID:26416970]
Abstract [show]
ATP-sensitive potassium channels (K-ATP channels) play a key role in adjusting the membrane potential to the metabolic state of cells. They result from the unique combination of two proteins: the sulfonylurea receptor (SUR), an ATP-binding cassette (ABC) protein, and the inward rectifier K(+) channel Kir6.2. Both subunits associate to form a heterooctamer (4 SUR/4 Kir6.2). SUR modulates channel gating in response to the binding of nucleotides or drugs and Kir6.2 conducts potassium ions. The activity of K-ATP channels varies with their localization. In pancreatic beta-cells, SUR1/Kir6.2 channels are partly active at rest while in cardiomyocytes SUR2A/Kir6.2 channels are mostly closed. This divergence of function could be related to differences in the interaction of SUR1 and SUR2A with Kir6.2. Three residues (E1305, I1310, L1313) located in the linker region between transmembrane domain 2 and nucleotide-binding domain 2 of SUR2A were previously found to be involved in the activation pathway linking binding of openers onto SUR2A and channel opening. To determine the role of the equivalent residues in the SUR1 isoform, we designed chimeras between SUR1 and the ABC transporter multidrug resistance-associated protein 1 (MRP1), and used patch clamp recordings on Xenopus oocytes to assess the functionality of SUR1/MRP1 chimeric K-ATP channels. Our results reveal that the same residues in SUR1 and SUR2A are involved in the functional association with Kir6.2, but they display unexpected side-chain specificities which could account for the contrasted properties of pancreatic and cardiac K-ATP channels.
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No. Sentence Comment
57 The amino acid composition of the constructs were as follows: SUR1S1M = SUR1(M1-V1313) + MRP1(V1261-F1341) + SUR1(R1394-K1582); SUR1S2M = SUR1 (M1-P1336) + MRP1(P1284-L1300) + SUR1(V1352-K1582); SUR1S3M = SUR1 with mutations N1338S, I1345V, S1351C, and V1352L; SUR1S4M = SUR1 with mutations K1337S, D1341Q, K1344R, Q1346E, and Q1348R; SUR1(QIL/VFY) = SUR1 with mutations Q1342V, I1347F, and L1350Y, SUR1S2M(VFY/QIL) = SUR1S2M with mutations V1290Q, F1295I, and Y1298L.
X
ABCC1 p.Phe1295Ile 26416970:57:449
status: NEW64 V1290Q, F1295I, and Y1298L, SUR1(QIL/III) = Q1342I, I1347I, and L1350I, SUR1(QIL/AAA) = Q1342A, I1347A, and L1350A, SUR1(QIL/GGG) = Q1342G, I1347G, and L1350G, SUR2A(EIL/III) = E1305I, I1310I, and L1313I, SUR2A(EIL/AAA) = E1305A, I1310A, and L1313A, SUR2A(EIL/GGG) = E1305G, I1310G, and L1313G.
X
ABCC1 p.Phe1295Ile 26416970:64:8
status: NEW