The synthetic aminoglycoside ELX-02 induces readthrough of G550X-CFTR producing super-functional protein that can be further enhanced by CFTR modulators.
American Journal Of Physiology. Lung Cellular And Molecular Physiology
Chen, Jianguo J; Thrasher, Kari K; Fu, Lianwu L; Wang, Wei W; Aghamohammadzadeh, Soheil S; Wen, Hui H; Tang, Liping L; Keeling, Kim M KM; Falk Libby, Emily E; Bedwell, David M DM; Rowe, Steven M SM
The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs.
International Journal Of Molecular Sciences
Sondo, Elvira E; Cresta, Federico F; Pastorino, Cristina C; Tomati, Valeria V; Capurro, Valeria V; Pesce, Emanuela E; Lena, Mariateresa M; Iacomino, Michele M; Baffico, Ave Maria AM; Coviello, Domenico D; Bandiera, Tiziano T; Zara, Federico F; Galietta, Luis J V LJV; Bocciardi, Renata R; Castellani, Carlo C; Pedemonte, Nicoletta N
Rescue of Mutant CFTR Trafficking Defect by the Investigational Compound MCG1516A.
Cells
Lopes-Pacheco, Miquéias M; Bacalhau, Mafalda M; Ramalho, Sofia S SS; Silva, Iris A L IAL; Ferreira, Filipa C FC; Carlile, Graeme W GW; Thomas, David Y DY; Farinha, Carlos M CM; Hanrahan, John W JW; Amaral, Margarida D MD
Rescue of Mutant CFTR Trafficking Defect by the Investigational Compound MCG1516A.
Cells
Lopes-Pacheco, Miquéias M; Bacalhau, Mafalda M; Ramalho, Sofia S SS; Silva, Iris A L IAL; Ferreira, Filipa C FC; Carlile, Graeme W GW; Thomas, David Y DY; Farinha, Carlos M CM; Hanrahan, John W JW; Amaral, Margarida D MD
Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies.
Cancer Gene Therapy
Denisova, Evgeniya E; Westphal, Dana D; Surowy, Harald M HM; Meier, Friedegund F; Hutter, Barbara B; Reifenberger, Julia J; Rütten, Arno A; Schulz, Alexander A; Sergon, Mildred M; Ziemer, Mirjana M; Brors, Benedikt B; Betz, Regina C RC; Redler, Silke S
Full Rescue of F508del-CFTR Processing and Function by CFTR Modulators Can Be Achieved by Removal of Two Regulatory Regions.
International Journal Of Molecular Sciences
Uliyakina, Inna I; Botelho, Hugo M HM; da Paula, Ana C AC; Afonso, Sara S; Lobo, Miguel J MJ; Felício, Verónica V; Farinha, Carlos M CM; Amaral, Margarida D MD
Identification of GLPG/ABBV-2737, a Novel Class of Corrector, Which Exerts Functional Synergy With Other CFTR Modulators.
Frontiers In Pharmacology
de Wilde, Gert G; Gees, Maarten M; Musch, Sara S; Verdonck, Katleen K; Jans, Mia M; Wesse, Anne-Sophie AS; Singh, Ashvani K AK; Hwang, Tzyh-Chang TC; Christophe, Thierry T; Pizzonero, Mathieu M; Van der Plas, Steven S; Desroy, Nicolas N; Cowart, Marlon M; Stouten, Pieter P; Nelles, Luc L; Conrath, Katja K
Folding Status Is Determinant over Traffic-Competence in Defining CFTR Interactors in the Endoplasmic Reticulum.
Cells
Santos, João D JD; Canato, Sara S; Carvalho, Ana S AS; Botelho, Hugo M HM; Aloria, Kerman K; Amaral, Margarida D MD; Matthiesen, Rune R; Falcao, Andre O AO; Farinha, Carlos M CM
ΔF508-CFTR Modulator Screen Based on Cell Surface Targeting of a Chimeric Nucleotide Binding Domain 1 Reporter.
Slas Discovery : Advancing Life Sciences R & D
Phuan, Puay-Wah PW; Veit, Guido G; Tan, Joseph-Anthony JA; Roldan, Ariel A; Finkbeiner, Walter E WE; Haggie, Peter M PM; Lukacs, Gergely L GL; Verkman, Alan S AS
Structural stability of purified human CFTR is systematically improved by mutations in nucleotide binding domain 1.
Biochimica Et Biophysica Acta. Biomembranes
Yang, Zhengrong Z; Hildebrandt, Ellen E; Jiang, Fan F; Aleksandrov, Andrei A AA; Khazanov, Netaly N; Zhou, Qingxian Q; An, Jianli J; Mezzell, Andrew T AT; Xavier, Bala M BM; Ding, Haitao H; Riordan, John R JR; Senderowitz, Hanoch H; Kappes, John C JC; Brouillette, Christie G CG; Urbatsch, Ina L IL
Partial rescue of F508del-cystic fibrosis transmembrane conductance regulator channel gating with modest improvement of protein processing, but not stability, by a dual-acting small molecule.
British Journal Of Pharmacology
Liu, Jia J; Bihler, Hermann H; Farinha, Carlos M CM; Awatade, Nikhil T NT; Romão, Ana M AM; Mercadante, Dayna D; Cheng, Yi Y; Musisi, Isaac I; Jantarajit, Walailak W; Wang, Yiting Y; Cai, Zhiwei Z; Amaral, Margarida D MD; Mense, Martin M; Sheppard, David N DN
Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell.
Nature Communications
Bagdany, Miklos M; Veit, Guido G; Fukuda, Ryosuke R; Avramescu, Radu G RG; Okiyoneda, Tsukasa T; Baaklini, Imad I; Singh, Jay J; Sovak, Guy G; Xu, Haijin H; Apaja, Pirjo M PM; Sattin, Sara S; Beitel, Lenore K LK; Roldan, Ariel A; Colombo, Giorgio G; Balch, William W; Young, Jason C JC; Lukacs, Gergely L GL
Deletion of Phenylalanine 508 in the First Nucleotide-binding Domain of the Cystic Fibrosis Transmembrane Conductance Regulator Increases Conformational Exchange and Inhibits Dimerization.
The Journal Of Biological Chemistry
Chong, P Andrew PA; Farber, Patrick J PJ; Vernon, Robert M RM; Hudson, Rhea P RP; Mittermaier, Anthony K AK; Forman-Kay, Julie D JD
Measurements of Functional Responses in Human Primary Lung Cells as a Basis for Personalized Therapy for Cystic Fibrosis.
Ebiomedicine
Awatade, Nikhil T NT; Uliyakina, Inna I; Farinha, Carlos M CM; Clarke, Luka A LA; Mendes, Karina K; Solé, Amparo A; Pastor, Juan J; Ramos, Maria Margarida MM; Amaral, Margarida D MD
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.
Science Translational Medicine
Veit, Guido G; Avramescu, Radu G RG; Perdomo, Doranda D; Phuan, Puay-Wah PW; Bagdany, Miklos M; Apaja, Pirjo M PM; Borot, Florence F; Szollosi, Daniel D; Wu, Yu-Sheng YS; Finkbeiner, Walter E WE; Hegedus, Tamas T; Verkman, Alan S AS; Lukacs, Gergely L GL
CFTR potentiators partially restore channel function to A561E-CFTR, a cystic fibrosis mutant with a similar mechanism of dysfunction as F508del-CFTR.
British Journal Of Pharmacology
Wang, Yiting Y; Liu, Jia J; Loizidou, Avgi A; Bugeja, Luc A LA; Warner, Ross R; Hawley, Bethan R BR; Cai, Zhiwei Z; Toye, Ashley M AM; Sheppard, David N DN; Li, Hongyu H
Revertant mutants modify, but do not rescue, the gating defect of the cystic fibrosis mutant G551D-CFTR.
The Journal Of Physiology
Xu, Zhe Z; Pissarra, Luísa S LS; Farinha, Carlos M CM; Liu, Jia J; Cai, Zhiwei Z; Thibodeau, Patrick H PH; Amaral, Margarida D MD; Sheppard, David N DN
Mechanism-based corrector combination restores ΔF508-CFTR folding and function.
Nature Chemical Biology
Okiyoneda, Tsukasa T; Veit, Guido G; Dekkers, Johanna F JF; Bagdany, Miklos M; Soya, Naoto N; Xu, Haijin H; Roldan, Ariel A; Verkman, Alan S AS; Kurth, Mark M; Simon, Agnes A; Hegedus, Tamas T; Beekman, Jeffrey M JM; Lukacs, Gergely L GL
Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules.
Proceedings Of The National Academy Of Sciences Of The United States Of America
Woodward, Owen M OM; Tukaye, Deepali N DN; Cui, Jinming J; Greenwell, Patrick P; Constantoulakis, Leeza M LM; Parker, Benjamin S BS; Rao, Anjana A; Köttgen, Michael M; Maloney, Peter C PC; Guggino, William B WB
Conformational changes relevant to channel activity and folding within the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator.
The Journal Of Biological Chemistry
Hudson, Rhea P RP; Chong, P Andrew PA; Protasevich, Irina I II; Vernon, Robert R; Noy, Efrat E; Bihler, Hermann H; An, Jian Li JL; Kalid, Ori O; Sela-Culang, Inbal I; Mense, Martin M; Senderowitz, Hanoch H; Brouillette, Christie G CG; Forman-Kay, Julie D JD
Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR.
Journal Of Molecular Biology
Aleksandrov, Andrei A AA; Kota, Pradeep P; Cui, Liying L; Jensen, Tim T; Alekseev, Alexey E AE; Reyes, Santiago S; He, Lihua L; Gentzsch, Martina M; Aleksandrov, Luba A LA; Dokholyan, Nikolay V NV; Riordan, John R JR
Phosphorylation-dependent 14-3-3 protein interactions regulate CFTR biogenesis.
Molecular Biology Of The Cell
Liang, Xiubin X; Da Paula, Ana Carina AC; Bozóky, Zoltán Z; Zhang, Hui H; Bertrand, Carol A CA; Peters, Kathryn W KW; Forman-Kay, Julie D JD; Frizzell, Raymond A RA
Requirements for efficient correction of ΔF508 CFTR revealed by analyses of evolved sequences.
Cell
Mendoza, Juan L JL; Schmidt, André A; Li, Qin Q; Nuvaga, Emmanuel E; Barrett, Tyler T; Bridges, Robert J RJ; Feranchak, Andrew P AP; Brautigam, Chad A CA; Thomas, Philip J PJ
Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function.
Cell
Rabeh, Wael M WM; Bossard, Florian F; Xu, Haijin H; Okiyoneda, Tsukasa T; Bagdany, Miklos M; Mulvihill, Cory M CM; Du, Kai K; di Bernardo, Salvatore S; Liu, Yuhong Y; Konermann, Lars L; Roldan, Ariel A; Lukacs, Gergely L GL
Human-mouse cystic fibrosis transmembrane conductance regulator (CFTR) chimeras identify regions that partially rescue CFTR-ΔF508 processing and alter its gating defect.
Proceedings Of The National Academy Of Sciences Of The United States Of America
Dong, Qian Q; Ostedgaard, Lynda S LS; Rogers, Christopher C; Vermeer, Daniel W DW; Zhang, Yuping Y; Welsh, Michael J MJ
Thermally unstable gating of the most common cystic fibrosis mutant channel (ΔF508): "rescue" by suppressor mutations in nucleotide binding domain 1 and by constitutive mutations in the cytosolic loops.
The Journal Of Biological Chemistry
Wang, Wei W; Okeyo, George O GO; Tao, Binli B; Hong, Jeong S JS; Kirk, Kevin L KL
The cystic fibrosis-causing mutation deltaF508 affects multiple steps in cystic fibrosis transmembrane conductance regulator biogenesis.
The Journal Of Biological Chemistry
Thibodeau, Patrick H PH; Richardson, John M JM; Wang, Wei W; Millen, Linda L; Watson, Jarod J; Mendoza, Juan L JL; Du, Kai K; Fischman, Sharon S; Senderowitz, Hanoch H; Lukacs, Gergely L GL; Kirk, Kevin K; Thomas, Philip J PJ