FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2972971354> ?p ?o ?g. }

• W2972971354 endingPage "19448" @default.
• W2972971354 startingPage "19440" @default.
• W2972971354 abstract "Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are the largest protein family causatively linked to neurodegenerative Charcot–Marie–Tooth (CMT) disease. Dominant mutations cause the disease, and studies of CMT disease-causing mutant glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase (TyrRS) showed their mutations create neomorphic structures consistent with a gain-of-function mechanism. In contrast, based on a haploid yeast model, loss of aminoacylation function was reported for CMT disease mutants in histidyl-tRNA synthetase (HisRS). However, neither that nor prior work of any CMT disease-causing aaRS investigated the aminoacylation status of tRNAs in the cellular milieu of actual patients. Using an assay that interrogated aminoacylation levels in patient cells, we investigated a HisRS-linked CMT disease family with the most severe disease phenotype. Strikingly, no difference in charged tRNA levels between normal and diseased family members was found. In confirmation, recombinant versions of 4 other HisRS CMT disease-causing mutants showed no correlation between activity loss in vitro and severity of phenotype in vivo. Indeed, a mutation having the most detrimental impact on activity was associated with a mild disease phenotype. In further work, using 3 independent biophysical analyses, structural opening (relaxation) of mutant HisRSs at the dimer interface best correlated with disease severity. In fact, the HisRS mutation in the severely afflicted patient family caused the largest degree of structural relaxation. These data suggest that HisRS-linked CMT disease arises from open conformation-induced mechanisms distinct from loss of aminoacylation." @default.
• W2972971354 created "2019-09-19" @default.
• W2972971354 creator A5002688120 @default.
• W2972971354 creator A5003648553 @default.
• W2972971354 creator A5024199145 @default.
• W2972971354 creator A5026512168 @default.
• W2972971354 creator A5026856074 @default.
• W2972971354 creator A5035678484 @default.
• W2972971354 creator A5038390604 @default.
• W2972971354 creator A5048002391 @default.
• W2972971354 creator A5053904206 @default.
• W2972971354 creator A5079163230 @default.
• W2972971354 creator A5081603031 @default.
• W2972971354 creator A5085476171 @default.
• W2972971354 date "2019-09-09" @default.
• W2972971354 modified "2023-09-26" @default.
• W2972971354 title "CMT disease severity correlates with mutation-induced open conformation of histidyl-tRNA synthetase, not aminoacylation loss, in patient cells" @default.
• W2972971354 cites W1840470014 @default.
• W2972971354 cites W1858745229 @default.
• W2972971354 cites W1977702947 @default.
• W2972971354 cites W1982067416 @default.
• W2972971354 cites W1982126789 @default.
• W2972971354 cites W1987711585 @default.
• W2972971354 cites W2005591340 @default.
• W2972971354 cites W2009061745 @default.
• W2972971354 cites W2028337350 @default.
• W2972971354 cites W2040724884 @default.
• W2972971354 cites W2050091361 @default.
• W2972971354 cites W2059003438 @default.
• W2972971354 cites W2060679106 @default.
• W2972971354 cites W2064713079 @default.
• W2972971354 cites W2065387868 @default.
• W2972971354 cites W2108093337 @default.
• W2972971354 cites W2117939646 @default.
• W2972971354 cites W2121303536 @default.
• W2972971354 cites W2124983865 @default.
• W2972971354 cites W2131918208 @default.
• W2972971354 cites W2140885472 @default.
• W2972971354 cites W2158265014 @default.
• W2972971354 cites W2167244555 @default.
• W2972971354 cites W2181472284 @default.
• W2972971354 cites W2182838444 @default.
• W2972971354 cites W2227237519 @default.
• W2972971354 cites W2343406672 @default.
• W2972971354 cites W2511931103 @default.
• W2972971354 cites W2600578427 @default.
• W2972971354 cites W2603775236 @default.
• W2972971354 cites W2617798208 @default.
• W2972971354 cites W2775729208 @default.
• W2972971354 cites W2788739753 @default.
• W2972971354 cites W2794157241 @default.
• W2972971354 cites W2794382336 @default.
• W2972971354 cites W2910096795 @default.
• W2972971354 doi "https://doi.org/10.1073/pnas.1908288116" @default.
• W2972971354 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6765236" @default.
• W2972971354 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31501329" @default.
• W2972971354 hasPublicationYear "2019" @default.
• W2972971354 type Work @default.
• W2972971354 sameAs 2972971354 @default.
• W2972971354 citedByCount "24" @default.
• W2972971354 countsByYear W29729713542020 @default.
• W2972971354 countsByYear W29729713542021 @default.
• W2972971354 countsByYear W29729713542022 @default.
• W2972971354 countsByYear W29729713542023 @default.
• W2972971354 crossrefType "journal-article" @default.
• W2972971354 hasAuthorship W2972971354A5002688120 @default.
• W2972971354 hasAuthorship W2972971354A5003648553 @default.
• W2972971354 hasAuthorship W2972971354A5024199145 @default.
• W2972971354 hasAuthorship W2972971354A5026512168 @default.
• W2972971354 hasAuthorship W2972971354A5026856074 @default.
• W2972971354 hasAuthorship W2972971354A5035678484 @default.
• W2972971354 hasAuthorship W2972971354A5038390604 @default.
• W2972971354 hasAuthorship W2972971354A5048002391 @default.
• W2972971354 hasAuthorship W2972971354A5053904206 @default.
• W2972971354 hasAuthorship W2972971354A5079163230 @default.
• W2972971354 hasAuthorship W2972971354A5081603031 @default.
• W2972971354 hasAuthorship W2972971354A5085476171 @default.
• W2972971354 hasBestOaLocation W29729713541 @default.
• W2972971354 hasConcept C104317684 @default.
• W2972971354 hasConcept C105951970 @default.
• W2972971354 hasConcept C126322002 @default.
• W2972971354 hasConcept C127716648 @default.
• W2972971354 hasConcept C143065580 @default.
• W2972971354 hasConcept C151238385 @default.
• W2972971354 hasConcept C153957851 @default.
• W2972971354 hasConcept C2779134260 @default.
• W2972971354 hasConcept C2779315393 @default.
• W2972971354 hasConcept C501734568 @default.
• W2972971354 hasConcept C54355233 @default.
• W2972971354 hasConcept C67705224 @default.
• W2972971354 hasConcept C71924100 @default.
• W2972971354 hasConcept C86803240 @default.
• W2972971354 hasConceptScore W2972971354C104317684 @default.
• W2972971354 hasConceptScore W2972971354C105951970 @default.
• W2972971354 hasConceptScore W2972971354C126322002 @default.
• W2972971354 hasConceptScore W2972971354C127716648 @default.
• W2972971354 hasConceptScore W2972971354C143065580 @default.
• W2972971354 hasConceptScore W2972971354C151238385 @default.

• next