ArticleProceedings of the National Academy of Sciences of the United States of America2005
ADP inhibits function of the ABC transporter cystic fibrosis transmembrane conductance regulator via its adenylate kinase activity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- The Potential Role of Creatine in Vascular Health.Nutrients · 2021Review
- Genetic Discovery of ATP-Sensitive KCirculation. Arrhythmia and electrophysiology · 2019Review
- Physiological and pharmacological characterization of the N1303K mutant CFTR.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2018Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.The Journal of biological chemistry · 2015Article
- ATP and AMP mutually influence their interaction with the ATP-binding cassette (ABC) adenylate kinase cystic fibrosis transmembrane conductance regulator (CFTR) at separate binding sites.The Journal of biological chemistry · 2013Article
- Demonstration of phosphoryl group transfer indicates that the ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) exhibits adenylate kinase activity.The Journal of biological chemistry · 2012Article
- K(ATP) channel action in vascular tone regulation: from genetics to diseases.Sheng li xue bao : [Acta physiologica Sinica] · 2012Review
- ATP-independent CFTR channel gating and allosteric modulation by phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- A mutation in CFTR modifies the effects of the adenylate kinase inhibitor Ap5A on channel gating.Biophysical journal · 2008Article
- Role of CFTR's intrinsic adenylate kinase activity in gating of the Cl(-) channel.Journal of bioenergetics and biomembranes · 2007Review
- Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- CFTR (ABCC7) is a hydrolyzable-ligand-gated channel.Pflugers Archiv : European journal of physiology · 2007Review
- High affinity ATP/ADP analogues as new tools for studying CFTR gating.The Journal of physiology · 2005Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
ADP interacts with the nucleotide-binding domains (NBDs) of the cystic fibrosis transmembrane conductance regulator (CFTR) to inhibit its Cl- channel activity. Because CFTR NBD2 has reversible adenylate kinase activity (ATP + AMP<==> ADP + ADP) that gates the channel, we asked whether ADP might inhibit current through this enzymatic activity. In adenylate kinases, binding of the two ADP molecules is cooperative. Consistent with this hypothesis, CFTR current inhibition showed positive cooperativity for ADP. We also found that ADP inhibition of current was attenuated when we prevented adenylate kinase activity with P1,P5-di(adenosine-5') pentaphosphate. Additional studies suggested that adenylate kinase-dependent inhibition involved phosphotransfer between two nucleotide diphosphates. These data indicate that the adenylate kinase reaction at NBD2 contributed to the inhibitory effect of ADP. Finding that ADP inhibits function via an adenylate kinase activity also helps explain the earlier observation that mutations that disrupt adenylate kinase activity also disrupt ADP inhibition. Thus, the results reveal a previously unrecognized mechanism by which ADP inhibits an ABC transporter.
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