ライフサイエンスコーパス: CFTR

1 CFTR activators have potential therapeutic indications i

2 CFTR channel gating is strictly coupled to phosphorylati

3 CFTR dysfunction affects innate immune pathways, generat

4 CFTR dysfunction mainly affects epithelial cells, althou

5 CFTR is a major prosecretory chloride channel at the ocu

6 CFTR is expressed in various cell types, including leuko

7 CFTR modulator therapy with tezacaftor-ivacaftor or ivac

8 CFTR sequencing demonstrated that she is a carrier for a

9 CFTR, the chloride channel mutated in cystic fibrosis (C

10 CFTR, the cystic fibrosis (CF) gene, encodes for the CFT

11 definition of the druggability of the 14-3-3-CFTR interface might offer an approach for cystic fibros

12 confirmed diagnosis of cystic fibrosis and a CFTR gating mutation on at least one allele from 15 hosp

13 eterozygous for the Phe508del mutation and a CFTR mutation associated with residual CFTR function.

14 eterozygous for the Phe508del deletion and a CFTR residual-function mutation.

15 However, both a CFTR corrector and potentiator enhanced activity of prot

16 ith a recently solved cryo-EM structure of a CFTR IWF state.

17 r alone or in combination with tezacaftor, a CFTR corrector, in 248 patients 12 years of age or older

18 -) currents, but unexpectedly also abrogates CFTR-mediated Cl(-) secretion and completely abolishes c

19 he most potent compound, 12, fully activated CFTR chloride conductance with EC50 approximately 30 nM,

20 3,5-triazine CFTRact-K089 (1) that activated CFTR with EC50 approximately 250 nM, which when delivere

21 These data indicate that H2S activates CFTR in Xenopus oocytes by inhibiting phosphodiesterase

22 ata provide insights into how loss of active CFTR at the membrane can have additional consequences be

23 ane Conductance Regulator (CFTR) gene affect CFTR protein biogenesis or its function as a chloride ch

24 t the C-terminal PDZ-domain of both A2BR and CFTR were crucial for this interaction, and that replaci

25 independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay

26 xtensively investigated, phosphorylation and CFTR-ATPase activity are still poorly understood.

27 by cAMP-dependent protein kinase A (PKA) and CFTR-ATPase activity.

28 gnificant ABCC transporters (MRP1, SUR1, and CFTR), determined by using single-particle cryo-electron

29 or (VX-770; Kalydeco), a clinically approved CFTR potentiator.

30 e proteostasis of other membrane proteins as CFTR and anthrax toxin receptor 2, two poor folders invo

31 To understand better CFTR function, we investigated the regulation of channel

32 o better understand the relationship between CFTR activity, airway microbiology and inflammation, and

33 (R)-BPO-27 fully blocked CFTR chloride conductance in epithelial cell cultures an

34 l information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism an

35 After complete CFTR sequencing, the method found three cryptic intronic

36 ulator (CFTR) gene, is capable of correcting CFTR-dependent chloride transport in cystic fibrosis hum

37 otal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structur

38 ack of an effect of C4 on I507-ATC DeltaF508 CFTR, but its additive effect in combination with VX-809

39 acted on VX-809-modified I507-ATC DeltaF508 CFTR.

40 C4 stabilized I507-ATT DeltaF508 CFTR band B, but without considerable biochemical and fu

41 ugs are being developed to correct DeltaF508 CFTR.

42 ansmembrane conductance regulator (DeltaF508 CFTR), the most frequent disease-associated mutant of CF

43 281, whereas others also corrected DeltaF508-CFTR.

44 /potentiator strategy, as used for DeltaF508-CFTR, to produce functional rescue of the truncated tran

45 the loss-of-function phenotype of DeltaF508-CFTR suggest that the ribosomal stalk modulates the fold

46 VAPB inhibited the degradation of DeltaF508-CFTR.

47 romyces cerevisiae phenocopies the DeltaF508-CFTR folding and trafficking defects.

48 eutic target for correction of the DeltaF508-CFTR folding defect.

49 these candidate genes enhanced the DeltaF508-CFTR functional expression at the apical PM in human CF

50 Pase and gating activity of dephosphorylated CFTR.

51 Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory therapy of d

52 itive model for VAP interactions that direct CFTR biogenesis.

53 mparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop t

54 that cigarette smoke not only downregulates CFTR activity but also inhibits BK channel function, the

55 context of its three upstream and downstream CFTR codons during G418-mediated suppression.

56 The presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent, exp

57 nels into a closed state and that endogenous CFTR in HBEs is affected by SMase activity.

58 Na2S enhanced CFTR stimulation by membrane-permeable 8Br-cAMP under in

59 orrector-potentiator therapy, which enhances CFTR transport to the membrane, have increased PTEN amou

60 -channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and mac

61 ht produce a greater benefit than expressing CFTR at wild-type levels when targeting small fractions

62 nsitive mutant cystic fibrosis channel (F508-CFTR) at the plasma membrane and after reconstitution in

63 concomitant functional inactivation of F508-CFTR are partially suppressed by constitutive activity o

64 contribute to functional maintenance of F508-CFTR by reshaping the conformational energetics of its f

65 SUMOylation, to selectively degrade F508del CFTR via the SUMO-targeted ubiquitin E3 ligase, RNF4 (RI

66 ic fibrosis patients with the common F508del-CFTR mutation.

67 PARP-16 and their ability to correct F508del-CFTR trafficking.

68 with cystic fibrosis homozygous for F508del-CFTR in an open-label study.

69 h cystic fibrosis and homozygous for F508del-CFTR, but it has not been assessed in younger patients.

70 tic fibrosis who were homozygous for F508del-CFTR.

71 with cystic fibrosis homozygous for F508del-CFTR.

72 rosis aged 6-11 years homozygous for F508del-CFTR.

73 ated autophagy in primary homozygous F508del-CFTR human bronchial epithelial (hBE) cells at submicrom

74 targets to correct basic defects in F508del-CFTR processing.

75 onic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, bu

76 y delayed deactivation of individual F508del-CFTR Cl(-) channels.

77 tor further destabilized full-length F508del-CFTR and accelerated channel deactivation.

78 ally stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F50

79 fied wild-type CFTR, the full-length F508del-CFTR was about 10 degrees C less thermostable.

80 nd ivacaftor deactivated macroscopic F508del-CFTR Cl(-) currents.

81 tability in a small subpopulation of F508del-CFTR Cl(-) channels but that the majority remain destabi

82 a membrane targeting and function of F508del-CFTR, but not of wild-type CFTR.

83 hese compounds on the instability of F508del-CFTR, the most common CF mutation.

84 Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deac

85 hose silencing significantly rescued F508del-CFTR activity, as indicated by enhanced anion transport

86 7 degrees C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane pa

87 f proteins whose suppression rescues F508del-CFTR function in bronchial epithelial cells.

88 nd the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy devel

89 ultaneously act as correctors of the F508del-CFTR folding defect and as broad-spectrum antivirals aga

90 g; eligible patients had to have the F508del-CFTR mutation on both alleles.

91 ears or older and homozygous for the F508del-CFTR mutation.

92 stic fibrosis and homozygous for the F508del-CFTR mutation.

93 To identify proteins associated with F508del-CFTR processing, we used a high-throughput functional as

94 CFTR and that this modification facilitates CFTR channel activation.

95 which likely forms the structural basis for CFTR's channel function.

96 side in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2

97 Our studies reveal a novel function for CFTR in antiviral immunity and demonstrate that the Delt

98 ARP-3 and -16 and that this is necessary for CFTR correction.

99 cidated structure-activity relationships for CFTR activation and identified substantially more potent

100 All patients were tested for CFTR genotype at screening; eligible patients had to hav

101 ummary, we have described a direct link from CFTR to Ezrin to PI3K/AKT signaling that is disrupted in

102 rously validated candidates using functional CFTR maturation and electrolyte transport assays in pola

103 ion in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria o

104 We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and

105 ographic lung disease in subjects with G551D-CFTR mutations.

106 CF transmembrane conductance regulator gene (CFTR).

107 ocyte expression system to shed light on how CFTR channel activity is reduced by SMase.

108 Human CFTR was heterologously expressed in Xenopus oocytes and

109 identical structures of zebrafish and human CFTR in the dephosphorylated, ATP-free form.

110 a 3.9 A structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomic

111 tigated the single-channel activity of human CFTR at different intracellular pH (pHi ) values.

112 st nucleotide-binding domain (NBD1) of human CFTR.

113 The human CFTR structure reveals a previously unresolved helix bel

114 Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditi

115 (iii) CFTR-ATPase activity is inversely related to CFTR anion

116 Synthesized analogs showed improved CFTR activation potency compared to 4 with EC50 down to

117 These findings suggest that improved CFTR trafficking could enhance P. aeruginosa clearance f

118 Riquelme et al. (2017) propose that improved CFTR trafficking could enhance P. aeruginosa clearance t

119 ith two ATP-binding sites, sites 1 and 2, in CFTR.

120 (-) transport given that neither a change in CFTR-dependent HCO3 (-) efflux nor Na(+) /HCO3 (-) cotra

121 turbing the gating conformational changes in CFTR's transmembrane domains (TMDs) without altering the

122 utations may impose combinatorial defects in CFTR channel biology.

123 ned action for 8 h and was without effect in CFTR-deficient mice.

124 Both mechanisms fail in CFTR(-/-) swine, suggesting that cystic fibrosis airways

125 osine- and forskolin-stimulated increases in CFTR-dependent transepithelial short-circuit current, in

126 ains the catalytically active ATPase site in CFTR.

127 f 21 (86%) known splice-altering variants in CFTR, a well-studied gene whose loss-of-function variant

128 absorption, while anion channels, including CFTR and Ca(2+)-activated chloride channels mediate anio

129 the apical side of cholangiocytes, including CFTR and SLC5A1, as well as reduced expression of IGF1.

130 In epithelia, an increased CFTR activity may correspond to a pro-secretory response

131 ology: it reduced inflammation and increased CFTR maturation, stability and activity.

132 nd report protein kinase A (PKA)-independent CFTR activation by calmodulin.

133 To study individual CFTR Cl(-) channels, we performed single-channel recordi

134 is not membrane delimited and that inhibited CFTR channels remain at the cell membrane, indicative of

135 ido-pyrrolo-oxazinedione (R)-BPO-27 inhibits CFTR chloride conductance with low-nanomolar potency.

136 sm by which sphingomyelin catalysis inhibits CFTR is not known but evidence suggests that it occurs i

137 ther, these data suggest that SMase inhibits CFTR channel function by locking channels into a closed

138 Sphingomyelinase C (SMase) inhibits CFTR chloride channel activity in multiple cell systems,

139 In humans and pigs lacking CFTR, unchecked H(+) secretion by the nongastric H(+)/K(

140 Here, we studied purified full-length CFTR protein using spectroscopic techniques to determine

141 Here, we show that Ezrin links CFTR and TLR4 signaling, and is necessary for PI3K/AKT s

142 used purified CFTR proteins and macroscopic CFTR Cl(-) currents.

143 e have previously shown that plasma membrane CFTR increases the surface density of the adenosine 2B r

144 el, results in the production of a misfolded CFTR protein, which has residual channel activity but is

145 Small-molecule CFTR activators increase tear secretion and prevent expe

146 Airway smooth muscle CFTR may represent a therapeutic target in CF and other

147 ing response to therapies directed at mutant CFTR.

148 oes not restore activity to Phe508del mutant CFTR.

149 Some mutant CFTR proteins show residual function and respond to the

150 tial physical interaction of FAU with mutant CFTR, leading to its degradation.

151 itical for the regulated channel activity of CFTR.

152 centration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFT

153 To understand better the kinetic basis of CFTR intraburst gating, we investigated the single-chann

154 The gating behaviour of CFTR is characterized by bursts of channel openings inte

155 be required to realize the full benefits of CFTR-targeting treatments.

156 e bicarbonate permeability (P HC O3/ Cl ) of CFTR, ANO1 and GlyR.

157 Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl(-)-oxalate exchange

158 ed on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy

159 s in length and weight with no correction of CFTR function.

160 By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphoryla

161 GYY4137 increased transmembrane currents of CFTR-expressing oocytes.

162 Phosphorylation of the regulatory domain of CFTR by protein kinase A (PKA) is required for its chann

163 ce between the catalytic and pore domains of CFTR and that this modification facilitates CFTR channel

164 tion of channel openings, the dysfunction of CFTR in CF and the action of drugs that repair CFTR gati

165 Evidence of CFTR binding to isolated calmodulin domains/lobes sugges

166 The extensive expression of CFTR in the enteric ganglia suggests that CFTR may play

167 Expression of CFTR protein and mRNA was detected in neurons of the gan

168 proper activation and membrane expression of CFTR.

169 ed secretory chloride channel independent of CFTR.

170 d inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is estab

171 nce suggests that it occurs independently of CFTR's regulatory "R" domain.

172 Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof

173 suppression to restore therapeutic levels of CFTR function.

174 ng insights into the molecular mechanisms of CFTR function.

175 e most frequent disease-associated mutant of CFTR, may affect protein biogenesis, structure, and func

176 p is the cause for the functional overlap of CFTR and Ca(2+)-dependent chloride transport.

177 ine-induced cAMP response in the presence of CFTR.

178 ing the HCO3(-) /Cl(-) permeability ratio of CFTR from 0.4 to 1.0 had little impact upon either the s

179 interaction between the regulatory region of CFTR and calmodulin, the major calcium signaling molecul

180 his study, we investigated the regulation of CFTR by H2S.

181 her, our data suggest that the regulation of CFTR intraburst gating is distinct from the ATP-dependen

182 Furthermore, removal of CFTR's PDZ binding motif (DeltaTRL) prevented actin rear

183 here, we investigate the direct response of CFTR to calmodulin-mediated calcium signaling.

184 s/lobes suggests a mechanism for the role of CFTR as a molecular hub.

185 ta highlight the critical regulatory role of CFTR in integrin activation by chemoattractants in monoc

186 erase activity and subsequent stimulation of CFTR by cAMP-dependent protein kinase A.

187 represent subtle changes in the structure of CFTR that are regulated by intracellular pH, in part, at

188 Intrinsic tryptophan fluorescence studies of CFTR showed that phosphorylation reduced iodide-mediated

189 tential utility of (R)-BPO-27 for therapy of CFTR-mediated secretory diarrheas.

190 Our results support the potential utility of CFTR-targeted activators as a novel prosecretory treatme

191 nteraction profile, but has little effect on CFTR expression.

192 Consistent with an effect on CFTR gating behavior, we found that altering gating kine

193 gest that they have counteracting effects on CFTR stability.

194 bed indirect effects of calcium signaling on CFTR or other calcium-activated chloride channels; here,

195 results highlight the importance of not only CFTR but also BK channel function in maintaining ASL hom

196 In addition, overexpressing CFTR might produce a greater benefit than expressing CFT

197 and apical Cl(-) and HCO3(-) permeabilities (CFTR), and reducing the activity of the basolateral Cl(-

198 Na2S potentiated CFTR stimulation by forskolin, but not that by IBMX.

199 ss entire CFTR populations, we used purified CFTR proteins and macroscopic CFTR Cl(-) currents.

200 the single-channel conductance (g) in R117H-CFTR, but found a approximately 13-fold lower open proba

201 rate that a synergistic improvement of R117H-CFTR function can be accomplished with a combined regime

202 acterizations of the gating defects of R117H-CFTR led to the conclusion that the mutation decreases P

203 pletely rectifies the gating defect of R117H-CFTR.

204 se reagents potentiate synergistically R117H-CFTR gating to a level that allows accurate assessments

205 ) domain, which was sufficient in regulating CFTR biogenesis.

206 ibrosis transmembrane conductance regulator (CFTR or ABCC7; i.e., G551D, S1251N, and G1349D), that we

207 ibrosis transmembrane conductance regulator (CFTR) activator with an EC50 of approximately 200 nM and

208 ibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic f

209 ibrosis transmembrane conductance regulator (CFTR) and dystrophin (DMD).

210 ibrosis transmembrane conductance regulator (CFTR) and large-conductance, Ca(2+)-activated, and volta

211 ibrosis transmembrane conductance regulator (CFTR) anion channel causes misfolding and premature degr

212 ibrosis transmembrane conductance regulator (CFTR) anion channels and solute carrier family 26 member

213 ibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease.

214 ibrosis transmembrane conductance regulator (CFTR) chloride channel occurs in these diarrheas.

215 ibrosis transmembrane conductance regulator (CFTR) chloride channel, leading to defective apical chlo

216 ibrosis transmembrane conductance regulator (CFTR) Cl(-) channel.

217 ibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial so

218 ibrosis transmembrane conductance regulator (CFTR) first cytosolic loop (CL1) and nucleotide binding

219 ibrosis transmembrane conductance regulator (CFTR) folding defect responsible for >90% of CF cases.

220 ibrosis Transmembrane Conductance Regulator (CFTR) gene affect CFTR protein biogenesis or its functio

221 ibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good

222 ibrosis transmembrane conductance regulator (CFTR) gene, is capable of correcting CFTR-dependent chlo

223 ibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, i

224 ibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecul

225 ibrosis transmembrane conductance regulator (CFTR) have blunted induction of PI3K/AKT signaling in re

226 ibrosis transmembrane conductance regulator (CFTR) in placebo-controlled studies and patients aged 6-

227 the CF transmembrane conductance regulator (CFTR) interacted directly and this interaction was neces

228 ibrosis transmembrane conductance regulator (CFTR) is a multidomain membrane protein that functions a

229 ibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from an ATP-binding ca

230 ibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that

231 ibrosis transmembrane conductance regulator (CFTR) is an ATP-gated Cl(-) channel defective in the gen

232 ibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator

233 ibrosis transmembrane conductance regulator (CFTR) is key for the optimization of therapeutics as wel

234 ibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation.

235 ibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in a

236 ibrosis transmembrane conductance regulator (CFTR) modulators tezacaftor (VX-661) and ivacaftor (VX-7

237 ibrosis transmembrane conductance regulator (CFTR) mutation in humans, DeltaF508, show increased morb

238 ibrosis transmembrane conductance regulator (CFTR) protein levels, and transepithelial resistance.

239 is (CF) transmembrane conductance regulator (CFTR) regulates bile secretion and other functions at th

240 ibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity.

241 ibrosis transmembrane conductance regulator (CFTR) that reduces Pseudomonas aeruginosa culture positi

242 ibrosis transmembrane conductance regulator (CFTR) W1282X PTC (a UGA codon) in the context of its thr

243 ibrosis transmembrane conductance regulator (CFTR), a 25% reduction of the single-channel conductance

244 ibrosis transmembrane conductance regulator (CFTR), F508del, is initiated by binding of the small hea

245 ibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stabili

246 ibrosis transmembrane conductance regulator (CFTR), which is defective in the genetic disease cystic

247 g in CF transmembrane conductance regulator (CFTR)-deficient organoids and by nasal potential differe

248 ibrosis transmembrane conductance regulator (CFTR).

249 ibrosis transmembrane conductance regulator (CFTR).

250 mon cystic fibrosis transmembrane regulator (CFTR) mutation that causes cystic fibrosis.

251 TR in CF and the action of drugs that repair CFTR gating defects.

252 and a CFTR mutation associated with residual CFTR function.

253 Several CFTR homology models have been developed using bacterial

254 of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types.

255 We tested the hypothesis that CFTR is expressed in airway smooth muscle and directly a

256 oke-induced channel dysfunction reveals that CFTR activity is downregulated via Smad3 signalling wher

257 evented actin rearrangement, suggesting that CFTR insertion in the plasma membrane results in local r

258 of CFTR in the enteric ganglia suggests that CFTR may play a role in the physiology of the innervatio

259 The CFTR-selective inhibitor, CFTRinh-172, modestly reduced

260 The effect of Na2S was blocked by the CFTR inhibitor CFTR_inh172, the adenylyl cyclase inhibit

261 n activity of the mutants was rescued by the CFTR potentiator, ivacaftor (VX-770).

262 cystic fibrosis and were homozygous for the CFTR Phe508del mutation.

263 cystic fibrosis and were homozygous for the CFTR Phe508del mutation.

264 e cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regul

265 ystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface

266 recessive disease caused by mutations in the CFTR gene that lead to progressive respiratory decline.

267 mitral valve prolapse, and mutations in the CFTR gene.

268 Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor,

269 Ivacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use f

270 d following G418-mediated suppression of the CFTR G542X UGA mutation.

271 ns show residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor a

272 the mutation K1250A or pretreating with the CFTR potentiator VX-770 (Ivacaftor) imparted resistance

273 us of A2BR with that of beta2AR removed this CFTR-dependency.

274 tics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also

275 y PKA and the minor contribution (</=10%) to CFTR-ATPase activity.

276 CFTR-ATPase activity is inversely related to CFTR anion flux.

277 in patients only, but apparently related to CFTR-contributed NPD level inversely.

278 es but these have low sequence similarity to CFTR and are not ion channels.

279 The major contribution (>/=90%) to the total CFTR-related ATP hydrolysis rate is due to phosphorylati

280 t rAAV-mediated gene transfer of a truncated CFTR functionally rescues the CF phenotype across the na

281 TR1281 channel activity to that of wild type CFTR.

282 al effects of this competition for wild-type CFTR and the major F508del mutant, hinting at potential

283 onfirmed that purified full-length wild-type CFTR is folded and structurally responsive to phosphoryl

284 Compared with purified wild-type CFTR, the full-length F508del-CFTR was about 10 degrees

285 nction of F508del-CFTR, but not of wild-type CFTR.

286 the open-time constant (tauo ) of wild-type CFTR.

287 P analogues in a similar manner as wild-type CFTR.

288 Among 1,423 unannotated CFTR disease-associated variants, the method identified

289 ents with CF independent of their underlying CFTR mutation.

290 s reinforces its relevance for understanding CFTR function.

291 We also found that some variant CFTR proteins generated by PTC suppression exhibit reduc

292 nt data are consistent with a model in which CFTR is in a closed conformation with two ATPs bound.

293 ction, but it is unknown the degree to which CFTR mutations account for sweat chloride variation.

294 Whilst CFTR's function as an ion channel has been well describe

295 Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determi

296 est that PTC suppression in combination with CFTR modulators may be beneficial for the treatment of C

297 ansporters, is cracked open, consistent with CFTR's unique channel function.

298 conformational dynamics and allostery within CFTR.

299 Here, we present the structure of zebrafish CFTR in the phosphorylated, ATP-bound conformation, dete

300 ce of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance