FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2059075829> ?p ?o ?g. }

• W2059075829 endingPage "e1000008" @default.
• W2059075829 startingPage "e1000008" @default.
• W2059075829 abstract "The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and cell biological studies show that the ΔF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the ΔF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-ΔF508 variants exhibited significantly higher folding probabilities than the original NBD1-ΔF508, thereby partially rescuing folding ability of the NBD1-ΔF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of NBD1-ΔF508 are essential information in correcting this pathogenic mutant." @default.
• W2059075829 created "2016-06-24" @default.
• W2059075829 creator A5031681098 @default.
• W2059075829 creator A5033490428 @default.
• W2059075829 creator A5038098410 @default.
• W2059075829 creator A5049400835 @default.
• W2059075829 date "2008-02-29" @default.
• W2059075829 modified "2023-10-16" @default.
• W2059075829 title "Diminished Self-Chaperoning Activity of the ΔF508 Mutant of CFTR Results in Protein Misfolding" @default.
• W2059075829 cites W1602887917 @default.
• W2059075829 cites W1969697265 @default.
• W2059075829 cites W1970440715 @default.
• W2059075829 cites W1987641460 @default.
• W2059075829 cites W1996779865 @default.
• W2059075829 cites W2018414056 @default.
• W2059075829 cites W2039599894 @default.
• W2059075829 cites W2065444910 @default.
• W2059075829 cites W2067308664 @default.
• W2059075829 cites W2070043042 @default.
• W2059075829 cites W2080746003 @default.
• W2059075829 cites W2082759836 @default.
• W2059075829 cites W2088118742 @default.
• W2059075829 cites W2092354764 @default.
• W2059075829 cites W2103879666 @default.
• W2059075829 cites W2118780761 @default.
• W2059075829 cites W2125713628 @default.
• W2059075829 cites W2129695352 @default.
• W2059075829 cites W2133107406 @default.
• W2059075829 cites W2137704498 @default.
• W2059075829 cites W2146335990 @default.
• W2059075829 cites W2161849629 @default.
• W2059075829 cites W2161983628 @default.
• W2059075829 cites W2164770290 @default.
• W2059075829 cites W4230115907 @default.
• W2059075829 doi "https://doi.org/10.1371/journal.pcbi.1000008" @default.
• W2059075829 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2265529" @default.
• W2059075829 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18463704" @default.
• W2059075829 hasPublicationYear "2008" @default.
• W2059075829 type Work @default.
• W2059075829 sameAs 2059075829 @default.
• W2059075829 citedByCount "49" @default.
• W2059075829 countsByYear W20590758292012 @default.
• W2059075829 countsByYear W20590758292013 @default.
• W2059075829 countsByYear W20590758292014 @default.
• W2059075829 countsByYear W20590758292015 @default.
• W2059075829 countsByYear W20590758292016 @default.
• W2059075829 countsByYear W20590758292017 @default.
• W2059075829 countsByYear W20590758292018 @default.
• W2059075829 countsByYear W20590758292019 @default.
• W2059075829 countsByYear W20590758292020 @default.
• W2059075829 countsByYear W20590758292021 @default.
• W2059075829 countsByYear W20590758292022 @default.
• W2059075829 crossrefType "journal-article" @default.
• W2059075829 hasAuthorship W2059075829A5031681098 @default.
• W2059075829 hasAuthorship W2059075829A5033490428 @default.
• W2059075829 hasAuthorship W2059075829A5038098410 @default.
• W2059075829 hasAuthorship W2059075829A5049400835 @default.
• W2059075829 hasBestOaLocation W20590758291 @default.
• W2059075829 hasConcept C104317684 @default.
• W2059075829 hasConcept C113027372 @default.
• W2059075829 hasConcept C118892022 @default.
• W2059075829 hasConcept C143065580 @default.
• W2059075829 hasConcept C167625842 @default.
• W2059075829 hasConcept C185592680 @default.
• W2059075829 hasConcept C204328495 @default.
• W2059075829 hasConcept C2777893369 @default.
• W2059075829 hasConcept C2778428886 @default.
• W2059075829 hasConcept C55493867 @default.
• W2059075829 hasConcept C86803240 @default.
• W2059075829 hasConcept C95444343 @default.
• W2059075829 hasConceptScore W2059075829C104317684 @default.
• W2059075829 hasConceptScore W2059075829C113027372 @default.
• W2059075829 hasConceptScore W2059075829C118892022 @default.
• W2059075829 hasConceptScore W2059075829C143065580 @default.
• W2059075829 hasConceptScore W2059075829C167625842 @default.
• W2059075829 hasConceptScore W2059075829C185592680 @default.
• W2059075829 hasConceptScore W2059075829C204328495 @default.
• W2059075829 hasConceptScore W2059075829C2777893369 @default.
• W2059075829 hasConceptScore W2059075829C2778428886 @default.
• W2059075829 hasConceptScore W2059075829C55493867 @default.
• W2059075829 hasConceptScore W2059075829C86803240 @default.
• W2059075829 hasConceptScore W2059075829C95444343 @default.
• W2059075829 hasIssue "2" @default.
• W2059075829 hasLocation W20590758291 @default.
• W2059075829 hasLocation W20590758292 @default.
• W2059075829 hasLocation W20590758293 @default.
• W2059075829 hasLocation W20590758294 @default.
• W2059075829 hasOpenAccess W2059075829 @default.
• W2059075829 hasPrimaryLocation W20590758291 @default.
• W2059075829 hasRelatedWork W2001758114 @default.
• W2059075829 hasRelatedWork W2047623797 @default.
• W2059075829 hasRelatedWork W2051216049 @default.
• W2059075829 hasRelatedWork W2053020161 @default.
• W2059075829 hasRelatedWork W2064468529 @default.
• W2059075829 hasRelatedWork W2070593573 @default.
• W2059075829 hasRelatedWork W2087263556 @default.
• W2059075829 hasRelatedWork W2137704498 @default.
• W2059075829 hasRelatedWork W2151837778 @default.

• next