ABCMdb

ABCC8 p.His1537Ala

Predicted by SNAP2:	A: D (91%), C: D (91%), D: D (95%), E: D (95%), F: D (91%), G: D (91%), I: D (91%), K: D (95%), L: D (91%), M: D (91%), N: D (91%), P: D (95%), Q: D (91%), R: D (91%), S: D (91%), T: D (75%), V: D (91%), W: D (95%), Y: D (91%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: 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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Publications
[hide] Mutations in the linker domain of NBD2 of SUR inhi... EMBO J. 2002 Aug 15;21(16):4250-8. Matsuo M, Dabrowski M, Ueda K, Ashcroft FM
Mutations in the linker domain of NBD2 of SUR inhibit transduction but not nucleotide binding.
EMBO J. 2002 Aug 15;21(16):4250-8., [PMID:12169627]

Abstract [show]
ATP-sensitive potassium (K(ATP)) channels are composed of an ATP-binding cassette (ABC) protein (SUR1, SUR2A or SUR2B) and an inwardly rectifying K(+) channel (Kir6.1 or Kir6.2). Like other ABC proteins, the nucleotide binding domains (NBDs) of SUR contain a highly conserved "signature sequence" (the linker, LSGGQ) whose function is unclear. Mutation of the conserved serine to arginine in the linker of NBD1 (S1R) or NBD2 (S2R) did not alter the ability of ATP or ADP (100 microM) to displace 8-azido-[(32)P]ATP binding to SUR1, or abolish ATP hydrolysis at NBD2. We co-expressed Kir6.2 with wild-type or mutant SUR in Xenopus oocytes and recorded the resulting currents in inside-out macropatches. The S1R mutation in SUR1, SUR2A or SUR2B reduced K(ATP) current activation by 100 microM MgADP, whereas the S2R mutation in SUR1 or SUR2B (but not SUR2A) abolished MgADP activation completely. The linker mutations also reduced (S1R) or abolished (S2R) MgATP-dependent activation of Kir6.2-R50G co-expressed with SUR1 or SUR2B. These results suggest that the linker serines are not required for nucleotide binding but may be involved in transducing nucleotide binding into channel activation.

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Sentences [show]
No. Sentence Comment
101 In contrast, the equivalent mutations in NBD2 (Q1426A and H1537A) did not affect functional expression. Login to comment
104 However, both the Q1426A and H1537A mutations reduced the ability of 100 mM MgADP to stimulate channel activity, resulting in a 50 T 5.2% (n = 5) block of Kir6.2/SUR1-Q1426A currents and a 30 T 2.6% (n = 11) block of Kir6.2/SUR1-H1537A currents (Figure 5). Login to comment
122 Mean KATP conductance recorded from patches excised from oocytes co-expressing Kir6.2 and either wild-type SUR1 or SUR containing mutations in the linker of NBD2 (SUR1-Q1426A and SUR1-H1537A). Login to comment
239 Mutations in the NBD2 linker were: SUR1-S1482R and SUR2-S1446R (S2R); SUR1-Q1426A, SUR1-H1537A. Login to comment