Cystic fibrosis in the Portuguese population: haplotype distribution and molecular pathology

1990 ◽  
Vol 85 (4) ◽  
pp. 404-405 ◽  
Author(s):  
Angela Duarte ◽  
Celeste Barreto ◽  
Luís Marques-Pinto ◽  
M. Carmo Tavares ◽  
Jorge Amil ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Pathology ◽  
Portuguese Population ◽  
Haplotype Distribution

Haplotype Distribution of and Linkage Disequilibrium Between Four Polymorphic Markers Near the CFTR Locus in Brazilian Cystic Fibrosis Patients

Human Biology ◽  
2005 ◽  
Vol 77 (6) ◽  
pp. 853-865 ◽  
Author(s):  
Giselda M. K. Cabello ◽  
Pedro H. Cabello ◽  
Jorge S. Lopez-Camelo ◽  
Juan C. Llerena ◽  
Octavio Fernandes
Keyword(s):  
Cystic Fibrosis ◽  
Linkage Disequilibrium ◽  
Polymorphic Markers ◽  
Haplotype Distribution

scholarly journals Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Márton A Simon ◽  
László Csanády
Keyword(s):  
Cystic Fibrosis ◽  
Hydrogen Bond ◽  
Molecular Pathology ◽  
Atp Hydrolysis ◽  
Salt Water ◽  
Anion Channel ◽  
Open Probability ◽  
Binding Domains ◽  
State Dependent ◽  
Cftr Mutations

The phosphorylation-activated anion channel CFTR is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived "flickery" nor in the long-lived 'interburst' closed state. Loss of this H-bond explains the strong gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design.

scholarly journals Molecular Typing and Exopolysaccharide Biosynthesis of Burkholderia cepacia Isolates from a Portuguese Cystic Fibrosis Center

2000 ◽  
Vol 38 (4) ◽  
pp. 1651-1655 ◽  
Author(s):  
João A. Richau ◽  
Jorge H. Leitão ◽  
Manuela Correia ◽  
Luís Lito ◽  
Maria José Salgado ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Epidemiological Survey ◽  
Treatment Center ◽  
Pulmonary Infections ◽  
Portuguese Population ◽  
Fragment Analysis ◽  
Exopolysaccharide Biosynthesis ◽  
Genomic Relatedness

This work describes the first epidemiological survey ofBurkholderia cepacia involved in pulmonary infections among the Portuguese population with cystic fibrosis (CF) who attended the major CF treatment Center in Lisbon at Sta. Maria Hospital from 1995 to the end of 1997. The characterization of the genomic relatedness of the isolates was based on the analysis of their ribopatterns (withEcoRI) followed by construction of a ribotype-based phylogenetic tree. This study was complemented with macrorestriction fragment analysis by pulsed-field gel electrophoresis. After optimization of the solid growth medium, we found that exopolysaccharide (EPS) production by B. cepacia CF isolates is not as rare a phenomenon as was thought before; indeed, 70% of the isolates examined were EPS producers.

The haplotype distribution of the ΔF508 mutation in cystic fibrosis families in Scotland

1990 ◽  
Vol 85 (4) ◽  
pp. 419-420 ◽  
Author(s):  
Iain McIntosh ◽  
Ann Curtis ◽  
Maria-Luz Lorenzo ◽  
Marion Keston ◽  
Annette J. Gilfillan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Haplotype Distribution

The molecular pathology of cystic fibrosis

1991 ◽  
Vol 1 (2) ◽  
pp. 80-82 ◽  
Author(s):  
Brandon Wainwright
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Pathology

scholarly journals Molecular pathology of a cystic fibrosis mutation is explained by loss of a hydrogen bond

2021 ◽  
Author(s):  
Márton A Simon ◽  
LászlÓ Csanády
Keyword(s):  
Cystic Fibrosis ◽  
Hydrogen Bond ◽  
Molecular Pathology ◽  
Atp Hydrolysis ◽  
Salt Water ◽  
Anion Channel ◽  
Open Probability ◽  
Binding Domains ◽  
State Dependent ◽  
Cftr Mutations

The phosphorylation-activated anion channel CFTR is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived "flickery" nor in the long-lived "interburst" closed state. Loss of this H-bond explains the entire gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design.

Sign in / Sign up

Export Citation Format

Share Document