Function of the second nucleotide‐binding fold in the CFTR chloride channel

FEBS Letters

Ma, Jianjie¹  Zerhusen, Bryan¹ 

[1] Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA

关键词: Cystic fibrosis;    HEK 293 cell;    Single channel recording;    Phosphorylation;    CFTR;    cystic fibrosis transmembrane conductance regulator;    PKA;    cAMP-dependent protein kinase;    PM;    plasma membrane;    NBF;    nucleotide-binding fold;    AMP-PNP;    5′-adenylylimidodiphosphate;    pS;    picosiemen;    DPC;    diphenylamine-2-carboxylate;   

DOI  :  10.1016/S0014-5793(99)01230-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

To test the role of nucleotide-binding fold (NBF) 2 and its interaction with the regulatory (R) domain in the function of the cystic fibrosis transmembrane conductance regulator (CFTR) channel, we used three deletion mutants of CFTR: ΔR(708-835), ΔNBF2(1185-1349) and ΔR-ΔNBF2. In lipid bilayers, ΔNBF2 channel activity is ATP- and cAMP-dependent protein kinase (PKA)-dependent, but unlike wild-type (wt) CFTR, it displays a reduced activity and insensitivity to 5′-adenylylimidodiphosphate (AMP-PNP). Both ΔR and ΔR-ΔNBF2 channels are PKA-independent, but ΔR activity is reduced whereas ΔR-ΔNBF2 activity is increased. Deletion of NBF2 from CFTR affects protein trafficking and channel gating kinetics. The data suggest that NBF2 could have inhibitory and stimulatory roles in CFTR activity by interaction with NBF1 directly or indirectly via the R domain.

【 授权许可】

Unknown