ArticleThe Journal of membrane biology2008
Mutations at arginine 352 alter the pore architecture of CFTR.
Article in The Journal of membrane biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Novel gain-of-function mutants identify a critical region within CFTR membrane-spanning domain 2 controlling cAMP-dependent and ATP-independent channel activation.Cellular and molecular life sciences : CMLS · 2024Article
- Two rare variants that affect the same amino acid in CFTR have distinct responses to ivacaftor.The Journal of physiology · 2024Article
- Acting on the CFTR Membrane-Spanning Domains Interface Rescues Some Misfolded Mutants.International journal of molecular sciences · 2022Article
- Molecular Dynamics and Theratyping in Airway and Gut Organoids Reveal R352Q-CFTR Conductance Defect.American journal of respiratory cell and molecular biology · 2022Article
- The molecular evolution of function in the CFTR chloride channel.The Journal of general physiology · 2021Article
- Electrophysiological Approaches for the Study of Ion Channel Function.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Discovering the chloride pathway in the CFTR channel.Cellular and molecular life sciences : CMLS · 2020Article
- Harmonizing Experimental Data with Modeling to Predict Membrane Protein Insertion in Yeast.Biophysical journal · 2019Article
- Molecular structure of the ATP-bound, phosphorylated human CFTR.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Combining theoretical and experimental data to decipher CFTR 3D structures and functions.Cellular and molecular life sciences : CMLS · 2018Article
- Structural mechanisms of CFTR function and dysfunction.The Journal of general physiology · 2018Review
- Transmembrane helical interactions in the CFTR channel pore.PLoS computational biology · 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
- Murine and human CFTR exhibit different sensitivities to CFTR potentiators.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Cystic Fibrosis Transmembrane Conductance Regulator (CFTR): CLOSED AND OPEN STATE CHANNEL MODELS.The Journal of biological chemistry · 2015Article
- The Fifth Transmembrane Segment of Cystic Fibrosis Transmembrane Conductance Regulator Contributes to Its Anion Permeation Pathway.Biochemistry · 2015Article
- A Point Mutation in the Ubiquitin Ligase RNF170 That Causes Autosomal Dominant Sensory Ataxia Destabilizes the Protein and Impairs Inositol 1,4,5-Trisphosphate Receptor-mediated Ca2+ Signaling.The Journal of biological chemistry · 2015Article
- Full-open and closed CFTR channels, with lateral tunnels from the cytoplasm and an alternative position of the F508 region, as revealed by molecular dynamics.Cellular and molecular life sciences : CMLS · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Arginine 352 (R352) in the sixth transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) previously was reported to form an anion/cation selectivity filter and to provide positive charge in the intracellular vestibule. However, mutations at this site have nonspecific effects, such as inducing susceptibility of endogenous cysteines to chemical modification. We hypothesized that R352 stabilizes channel structure and that charge-destroying mutations at this site disrupt pore architecture, with multiple consequences. We tested the effects of mutations at R352 on conductance, anion selectivity and block by the sulfonylurea drug glipizide, using recordings of wild-type and mutant channels. Charge-altering mutations at R352 destabilized the open state and altered both selectivity and block. In contrast, R352K-CFTR was similar to wild-type. Full conductance state amplitude was similar to that of wild-type CFTR in all mutants except R352E, suggesting that R352 does not itself form an anion coordination site. In an attempt to identify an acidic residue that may interact with R352, we found that permeation properties were similarly affected by charge-reversing mutations at D993. Wild-type-like properties were rescued in R352E/D993R-CFTR, suggesting that R352 and D993 in the wild-type channel may interact to stabilize pore architecture. Finally, R352A-CFTR was sensitive to modification by externally applied MTSEA+, while wild-type and R352E/D993R-CFTR were not. These data suggest that R352 plays an important structural role in CFTR, perhaps reflecting its involvement in forming a salt bridge with residue D993.
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