ArticleProceedings of the National Academy of Sciences of the United States of America2008
Evolutionary and functional divergence between the cystic fibrosis transmembrane conductance regulator and related ATP-binding cassette transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- Comparing ATPase activity of ATP-binding cassette subfamily C member 4, lamprey CFTR, and human CFTR using an antimony-phosphomolybdate assay.Frontiers in pharmacology · 2024Article
- Research progress on the molecular structure, function, and application in tumor therapy of zinc transporter ZIP4.International journal of biological sciences · 2024Review
- Mutation accumulation in H. sapiens F508del CFTR countermands dN/dS type genomic analysis.PloS one · 2024Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- TwinCons: Conservation score for uncovering deep sequence similarity and divergence.PLoS computational biology · 2021Article
- Pharmacological approaches for targeting cystic fibrosis nonsense mutations.European journal of medicinal chemistry · 2020Review
- An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.Developmental cell · 2019Article
- Cystic fibrosis transmembrane conductance regulator (CFTR): Making an ion channel out of an active transporter structure.Channels (Austin, Tex.) · 2018Review
- Comparative transcriptomes and reciprocal best hit analysis revealed potential pigment genes in two color forms of Tetranychus urticae.Experimental & applied acarology · 2017Article
- Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.The Journal of biological chemistry · 2017Article
- Transmembrane helical interactions in the CFTR channel pore.PLoS computational biology · 2017Article
- Genome-wide analysis of ATP-binding cassette (ABC) transporters in the sweetpotato whitefly, Bemisia tabaci.BMC genomics · 2017Article
- Electrostatic tuning of the pre- and post-hydrolytic open states in CFTR.The Journal of general physiology · 2017Article
- Architecture and functional properties of the CFTR channel pore.Cellular and molecular life sciences : CMLS · 2017Review
- Formation of a Chloride-conducting State in the Maltose ATP-binding Cassette (ABC) Transporter.The Journal of biological chemistry · 2016Article
- Cytoplasmic pathway followed by chloride ions to enter the CFTR channel pore.Cellular and molecular life sciences : CMLS · 2016Article
- A Pore Idea: the ion conduction pathway of TMEM16/ANO proteins is composed partly of lipid.Pflugers Archiv : European journal of physiology · 2016Review
- The Role of Eukaryotic and Prokaryotic ABC Transporter Family in Failure of Chemotherapy.Frontiers in pharmacology · 2016Review
- The Fifth Transmembrane Segment of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Its Anion Permeation Pathway.Biochemistry · 2015Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily, an ancient family of proteins found in all phyla. In nearly all cases, ABC proteins are transporters that couple the hydrolysis of ATP to the transmembrane movement of substrate via an alternating access mechanism. In contrast, CFTR is best known for its activity as an ATP-dependent chloride channel. We asked why CFTR, which shares the domain architecture of ABC proteins that function as transporters, exhibits functional divergence. We compared CFTR protein sequences to those of other ABC transporters, which identified the ABCC4 proteins as the closest mammalian paralogs, and used statistical analysis of the CFTR-ABCC4 multiple sequence alignment to identify the specific domains and residues most likely to be involved in the evolutionary transition from transporter to channel activity. Among the residues identified as being involved in CFTR functional divergence, by virtue of being both CFTR-specific and conserved among all CFTR orthologs, was R352 in the sixth transmembrane helix (TM6). Patch-clamp experiments show that R352 interacts with D993 in TM9 to stabilize the open-channel state; D993 is absolutely conserved between CFTRs and ABCC4s. These data suggest that CFTR channel activity evolved, at least in part, by converting the conformational changes associated with binding and hydrolysis of ATP, as are found in true ABC Transporters, into an open permeation pathway by means of intraprotein interactions that stabilize the open state. This analysis sets the stage for understanding the evolutionary and functional relationships that make CFTR a unique ABC transporter protein.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.