R-Domain Phosphorylation by Protein Kinase A Stimulates Dissociation of Unhydrolyzed ATP from the First Nucleotide-Binding Site of the Cystic Fibrosis Transmembrane Conductance Regulator
Biochemistry, ISSN: 1520-4995, Vol: 57, Issue: 34, Page: 5073-5075
2018
- 5Citations
- 11Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations5
- Citation Indexes5
- CrossRef3
- Captures11
- Readers11
- 11
Article Description
The cystic fibrosis transmembrane conductance regulator (CFTR) is an asymmetric ATP-binding cassette transporter in which ATP hydrolysis occurs only at the second of the two composite nucleotide-binding sites whereas there are noncanonical substitutions of key catalytic residues in the first site. Therefore, in widely accepted models of CFTR function, ATP is depicted as remaining bound at the first site while it is hydrolyzed at the second site. However, the long lifetime of ATP at nucleotide-binding domain 1 (NBD1) had been measured under conditions where the channel had not been activated by phosphorylation. Here we show that phosphorylation by protein kinase A (PKA), obligatory for channel activation, strongly accelerates dissociation of the unhydrolyzed ATP from NBD1 of both full-length and NBD2-deleted CFTR. This stimulation of nucleotide release results from phosphorylation of the CFTR regulatory domain (residues 634-835) (R-domain). Mimicking phosphorylation by mutating the eight phosphorylation sites in the R-domain (8SE) has the same robust effect on accelerating the dissociation of ATP from NBD1. These findings provide new insight into relationships between R-domain phosphorylation and ATP binding and hydrolysis, the two main CFTR regulatory pathways.
Bibliographic Details
American Chemical Society (ACS)
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