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Science 12 July 1991:
Vol. 253. no. 5016, pp. 205 - 207
DOI: 10.1126/science.1712985
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Articles

Science, Vol 253, Issue 5016, 205-207
Copyright © 1991 by American Association for the Advancement of Science

articles

Effect of deleting the R domain on CFTR-generated chloride channels

DP Rich, RJ Gregory, MP Anderson, P Manavalan, AE Smith, and MJ Welsh

Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.

The cystic fibrosis transmembrane conductance regulator (CFTR), which forms adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, is defective in patients with cystic fibrosis. This protein contains two putative nucleotide binding domains (NBD1 and NBD2) and an R domain. CFTR in which the R domain was deleted (CFTR delta R) conducted chloride independently of the presence of cAMP. However, sites within CFTR other than those deleted also respond to cAMP, because the chloride current of CFTR delta R increased further in response to cAMP stimulation. In addition, deletion of the R domain suppressed the inactivating effect of a mutation in NBD2 (but not NBD1), a result which suggests that NBD2 interacts with the channel through the R domain.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)