ABCMdb

PMID: 18990670

Aittoniemi J, Fotinou C, Craig TJ, de Wet H, Proks P, Ashcroft FM
Review. SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator.
Philos Trans R Soc Lond B Biol Sci. 2009 Jan 27;364(1514):257-67., [PubMed]

Sentences

No. Mutations Sentence Comment

97 ABCC8 p.Phe132Leu ABCC8 p.Tyr195Glu Co-immunoprecipitation (but not necessarily surface trafficking) is abolished by mutation of F132L in CL2 (Proks et al. 2006a) and of Y195E at the start of CL3 (figure 2). Login to comment 98 ABCC8 p.Phe132Leu ABCC8 p.Tyr195Glu Co-immunoprecipitation (but not necessarily surface trafficking) is abolished by mutation of F132L in CL2 (Proks et al. 2006a) and of Y195E at the start of CL3 (figure 2). Login to comment 101 ABCC8 p.Phe132Leu For example, the F132L mutation in SUR1 disrupts the physical binding of Kir6.2 and TMD0 (Proks et al. 2007). Login to comment 102 ABCC8 p.Phe132Leu For example, the F132L mutation in SUR1 disrupts the physical binding of Kir6.2 and TMD0 (Proks et al. 2007). Login to comment 103 ABCC8 p.Phe132Leu This indicates that the F132L mutation must disrupt an inhibitory interaction between Kir6.2 and TMD0, leaving a stimulatory interaction intact. Login to comment 104 ABCC8 p.Phe132Leu This indicates that the F132L mutation must disrupt an inhibitory interaction between Kir6.2 and TMD0, leaving a stimulatory interaction intact. Login to comment 122 ABCC8 p.Tyr195Glu 0 20 40 60 80 100 TMD0 + 6.2࢞C TMD0 Y195E + 6.2࢞C binding (% WT) Figure 2. Login to comment 123 ABCC8 p.Tyr195Glu ABCC8 p.Tyr195Glu 0 20 40 60 80 100 TMD0 + 6.2∆C TMD0 Y195E + 6.2∆C binding(%WT) Figure 2. Login to comment 124 ABCC8 p.Tyr195Glu Binding of TMD0 to Kir6.2DC-effect of the Y195E mutation. Login to comment 169 ABCC8 p.Phe132Leu Only one mutation (F132L) has been shown to act this way to date (Proks et al. 2006a, 2007). Login to comment 171 ABCC8 p.Phe132Leu The F132L mutation increases the duration of the bursts of the KATP channel openings and reduces the frequency and duration of the interburst closed states. Login to comment 172 ABCC8 p.Phe132Leu Only one mutation (F132L) has been shown to act this way to date (Proks et al. 2006a, 2007). Login to comment 174 ABCC8 p.Phe132Leu The F132L mutation increases the duration of the bursts of the KATP channel openings and reduces the frequency and duration of the interburst closed states. Login to comment 182 ABCC8 p.Ile1424Val The I1425V mutation in NBD2 also shows greater Mg-nucleotide-dependent stimulation of the channel activity (Babenko et al. 2006; I1424V in their notation). Login to comment 184 ABCC8 p.His1023Tyr ABCC8 p.Leu225Pro Finally, some mutations (e.g. H1023Y in TM12, Babenko et al. 2006; L225P in CL3, Masia et al. 2007) enhance Mg-nucleotide activation by unknown mechanisms. Login to comment 185 ABCC8 p.Phe132Leu ABCC8 p.Asp212Ile ABCC8 p.Thr229Ile ABCC8 p.Asn72Ser ABCC8 p.Pro207Ser ABCC8 p.Pro45Leu ABCC8 p.Asp212Asn ABCC8 p.Ile1424Val ABCC8 p.Pro206Leu Such naturally occurring mutations TNDM PNDM DEND TNDM PNDM DEND iDEND WT P206L D212N P45L N72S P207S E208K+Y263D D212I T229I A1185E V1522L+Y229I F132L 0 0.05 0.10 0.15 fractionofcurrentremaining in3mMMgATP(a) (b) (i) (ii) Figure 4. Login to comment 187 ABCC8 p.His1023Tyr ABCC8 p.Leu225Pro Finally, some mutations (e.g. H1023Y in TM12, Babenko et al. 2006; L225P in CL3, Masia et al. 2007) enhance Mg-nucleotide activation by unknown mechanisms. Login to comment 188 ABCC8 p.Phe132Leu ABCC8 p.Asp212Ile ABCC8 p.Thr229Ile ABCC8 p.Asn72Ser ABCC8 p.Pro207Ser ABCC8 p.Pro45Leu ABCC8 p.Asp212Asn ABCC8 p.Pro206Leu Such naturally occurring mutations TNDM PNDM DEND TNDM PNDM DEND iDEND WT P206L D212N P45L N72S P207S E208K+Y263D D212I T229I A1185E V1522L+Y229I F132L 0 0.05 0.10 0.15 fraction of current remaining in 3 mM MgATP (a) (b) (i) (ii) Figure 4. Login to comment 204 ABCC8 p.Phe132Leu ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp ABCC8 p.His1023Tyr ABCC8 p.Leu438Phe ABCC8 p.Arg306His ABCC8 p.Asp212Ile ABCC8 p.Asp209Glu ABCC8 p.Thr229Ile ABCC8 p.Leu582Val ABCC8 p.Tyr263Asp ABCC8 p.Asn72Ser ABCC8 p.Cys435Arg ABCC8 p.Val86Gly ABCC8 p.Glu382Lys ABCC8 p.Leu213Arg ABCC8 p.Val324Met ABCC8 p.Glu208Lys ABCC8 p.Pro207Ser ABCC8 p.Pro45Leu ABCC8 p.Gln211Lys ABCC8 p.Leu225Pro ABCC8 p.Ala269Asp (a) (b) P45L N72S F132L NH2 A90V V86G COOHL135P exoplasmic cytoplasmic Walker A Walker A linker Walker B linker Walker B V324M E382K C435R L438F L582V R826W H1023Y N1122D R1183Q A1185E R1314H E1327K R1380 L I1425V V1524 L P207S E208K Q211K D212I/N L225P T229I Y263D A269D R306H D209E L213R TMD0 TMD1 TMD2 NBD1 NBD2 CL3 linker site 1 site 2 NBD1 NBD2 R826W R1380 L E1327K I1425V V1524 L Figure 5. Login to comment 207 ABCC8 p.Phe132Leu ABCC8 p.Ala90Val ABCC8 p.Asn1122Asp ABCC8 p.His1023Tyr ABCC8 p.Leu135Pro ABCC8 p.Leu438Phe ABCC8 p.Arg306His ABCC8 p.Asp212Ile ABCC8 p.Asp209Glu ABCC8 p.Thr229Ile ABCC8 p.Leu582Val ABCC8 p.Tyr263Asp ABCC8 p.Asn72Ser ABCC8 p.Cys435Arg ABCC8 p.Val86Gly ABCC8 p.Glu382Lys ABCC8 p.Leu213Arg ABCC8 p.Val324Met ABCC8 p.Glu208Lys ABCC8 p.Pro207Ser ABCC8 p.Pro45Leu ABCC8 p.Gln211Lys ABCC8 p.Leu225Pro ABCC8 p.Ala269Asp (a) (b) P45L N72S F132L NH2 A90V V86G COOH L135P exoplasmic cytoplasmic Walker A Walker A linker Walker B linker Walker B V324M E382K C435R L438F L582V R826W H1023Y N1122D R1183Q A1185E R1314H E1327K R1380 L I1425V V1524 L P207S E208K Q211K D212I/N L225P T229I Y263D A269D R306H D209E L213R TMD0 TMD1 TMD2 NBD1 NBD2 CL3 linker site 1 site 2 NBD1 NBD2 R826W R1380 L E1327K I1425V V1524 L Figure 5. Login to comment