FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3158278008> ?p ?o ?g. }

• W3158278008 abstract "Several important cellular processes, including transcription, nucleotide excision repair and cell cycle control are mediated by the multifaceted interplay of subunits within the general transcription factor II H (TFIIH). A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these pathways. This becomes especially important in the context of severe diseases like xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, that arise from single point mutations in some of the TFIIH subunits. In an attempt to structurally characterize the TFIIH complex, we harnessed the qualities of the eukaryotic thermophile Chaetomium thermophilum, a remarkable fungus, which has only recently been recognized as a novel model organism. Homologues of TFIIH from C. thermophilum were expressed in E. coli, purified to homogeneity and subsequently utilized for crystallization trials and biochemical studies.The results of the present work include the first crystal structure of the p34 subunit of TFIIH, comprising the N-terminal domain of the protein. The structure revealed a von Willebrand Factor A (vWA) like fold, which is generally known to be involved in a multitude of protein-protein interactions. Structural comparison allowed to delineate similarities as well as differences to already known vWA domains, providing insight into the role of p34 within TFIIH. These results indicate that p34 assumes the role of a structural scaffold for other TFIIH subunits via its vWA domain, while likely serving additional functions, which are mediated through its C-terminal zinc binding domain and are so far unknown.Within TFIIH p34 interacts strongly with the p44 subunit, a positive regulator of the XPD helicase, which is required for regulation of RNA Polymerase II mediated transcription and essential for eukaryotic nucleotide excision repair. Based on the p34 vWA structure putative protein-protein interfaces were analyzed and binding sites for the p34 p44 interaction suggested. Continuous crystallization efforts then led to the first structure of a p34 p44 minimal complex, comprising the N-terminal vWA domain of p34 and the C-terminal C4C4 RING domain of p44. The structure of the p34 p44 minimal complex verified the previous hypothesis regarding the involved binding sites. In addition, careful analysis of the complex interface allowed to identify critical residues, which were subsequently mutated and analyzed with respect to their significance in mediating the p34 p44 interaction, by analytical size exclusion chromatography, electrophoretic mobility shift assays and isothermal titration calorimetry. The structure of the p34 p44 complex also revealed a binding mode of the p44 C4C4 RING domain, which differed from that of other known RING domains in several aspects, supporting the hypothesis that p44 contains a novel variation of this domain." @default.
• W3158278008 created "2021-05-10" @default.
• W3158278008 creator A5000041814 @default.
• W3158278008 date "2017-01-01" @default.
• W3158278008 modified "2023-09-24" @default.
• W3158278008 title "Structural Characterization of the TFIIH Subunits p34 and p44 from C. thermophilum" @default.
• W3158278008 hasPublicationYear "2017" @default.
• W3158278008 type Work @default.
• W3158278008 sameAs 3158278008 @default.
• W3158278008 citedByCount "0" @default.
• W3158278008 crossrefType "journal-article" @default.
• W3158278008 hasAuthorship W3158278008A5000041814 @default.
• W3158278008 hasConcept C104292427 @default.
• W3158278008 hasConcept C104317684 @default.
• W3158278008 hasConcept C104451858 @default.
• W3158278008 hasConcept C134935766 @default.
• W3158278008 hasConcept C138885662 @default.
• W3158278008 hasConcept C179926584 @default.
• W3158278008 hasConcept C41895202 @default.
• W3158278008 hasConcept C54355233 @default.
• W3158278008 hasConcept C552990157 @default.
• W3158278008 hasConcept C55493867 @default.
• W3158278008 hasConcept C56149667 @default.
• W3158278008 hasConcept C86803240 @default.
• W3158278008 hasConcept C95444343 @default.
• W3158278008 hasConceptScore W3158278008C104292427 @default.
• W3158278008 hasConceptScore W3158278008C104317684 @default.
• W3158278008 hasConceptScore W3158278008C104451858 @default.
• W3158278008 hasConceptScore W3158278008C134935766 @default.
• W3158278008 hasConceptScore W3158278008C138885662 @default.
• W3158278008 hasConceptScore W3158278008C179926584 @default.
• W3158278008 hasConceptScore W3158278008C41895202 @default.
• W3158278008 hasConceptScore W3158278008C54355233 @default.
• W3158278008 hasConceptScore W3158278008C552990157 @default.
• W3158278008 hasConceptScore W3158278008C55493867 @default.
• W3158278008 hasConceptScore W3158278008C56149667 @default.
• W3158278008 hasConceptScore W3158278008C86803240 @default.
• W3158278008 hasConceptScore W3158278008C95444343 @default.
• W3158278008 hasLocation W31582780081 @default.
• W3158278008 hasOpenAccess W3158278008 @default.
• W3158278008 hasPrimaryLocation W31582780081 @default.
• W3158278008 hasRelatedWork W1967146498 @default.
• W3158278008 hasRelatedWork W1967969318 @default.
• W3158278008 hasRelatedWork W1969688989 @default.
• W3158278008 hasRelatedWork W1983603366 @default.
• W3158278008 hasRelatedWork W1998889870 @default.
• W3158278008 hasRelatedWork W1999825561 @default.
• W3158278008 hasRelatedWork W2018133293 @default.
• W3158278008 hasRelatedWork W2057512204 @default.
• W3158278008 hasRelatedWork W2069063444 @default.
• W3158278008 hasRelatedWork W2097207357 @default.
• W3158278008 hasRelatedWork W2108026067 @default.
• W3158278008 hasRelatedWork W2119960401 @default.
• W3158278008 hasRelatedWork W2123144861 @default.
• W3158278008 hasRelatedWork W2154723040 @default.
• W3158278008 hasRelatedWork W2520601514 @default.
• W3158278008 hasRelatedWork W2742864212 @default.
• W3158278008 hasRelatedWork W2766148605 @default.
• W3158278008 hasRelatedWork W2803266032 @default.
• W3158278008 hasRelatedWork W2977977919 @default.
• W3158278008 hasRelatedWork W2979262335 @default.
• W3158278008 isParatext "false" @default.
• W3158278008 isRetracted "false" @default.
• W3158278008 magId "3158278008" @default.
• W3158278008 workType "article" @default.