FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387357363> ?p ?o ?g. }

• W4387357363 abstract "ABSTRACT Legionella pneumophila is a bacterial pathogen ubiquitous in natural and man-made aquatic environments, where it replicates in protozoa. Its intracellular life cycle depends on the establishment of a Legionella -containing vacuole (LCV) where the bacteria replicate. To form the LCV, L. pneumophila depends on a type-4 secretion system that secretes more than 300 proteins in the host cell. Among these is RomA that encodes an N-terminal catalytic methyltransferase domain with a SET fold and a C-terminal domain containing six ankyrin repeats. We have reported that the SET domain has histone methyltransferase activity and specifically methylates lysine 14 of histone H3 during infection; however, the role of the ankyrin repeats is unknown. Here, we report the structure of RomA co-crystallized with a 15-mer peptide corresponding to the N-terminal tail of histone H3 at 2.2 Å. This structure revealed that the N-terminal arm of the peptide from Thr3-Ala7 binds to the ankyrin repeat domain and the C-terminal arm from Gly13-Arg17 and interacts with the SET domain, inserting Lys14 into the active site for methylation. Importantly, the interactions of the five N-terminal residues of the H3-peptide with the ankyrin domains account for ~50% of the peptide-RomA contacts, predicting that the ankyrin domains of RomA are essential for histone H3 binding and subsequent lysine methylation. In vitro enzymatic activity and binding assays confirmed these predictions. Thus, the six ankyrin domains are essential for chromatin binding, thereby allowing the SET domain to fulfill its histone transferase activity and to modify the host chromatin to the advantage of the pathogen. IMPORTANCE Legionella pneumophila is an intracellular bacterium responsible of Legionnaires’ disease, a severe pneumonia that is often fatal when not treated promptly. The pathogen’s ability to efficiently colonize the host resides in its ability to replicate intracellularly. Essential for intracellular replication is translocation of many different protein effectors via a specialized secretion system. One of them, called RomA, binds and directly modifies the host chromatin at a unique site (tri-methylation of lysine 14 of histone H3 [H3K14me]). However, the molecular mechanisms of binding are not known. Here, we resolve this question through structural characterization of RomA together with the H3 peptide. We specifically reveal an active role of the ankyrin repeats located in its C-terminal in the interaction with the histone H3 tail. Indeed, without the ankyrin domains, RomA loses its ability to act as histone methyltransferase. These results discover the molecular mechanisms by which a bacterial histone methyltransferase that is conserved in L. pneumophila strains acts to modify chromatin." @default.
• W4387357363 created "2023-10-06" @default.
• W4387357363 creator A5005759921 @default.
• W4387357363 creator A5029808456 @default.
• W4387357363 creator A5040472662 @default.
• W4387357363 creator A5049173678 @default.
• W4387357363 creator A5049223590 @default.
• W4387357363 creator A5075868129 @default.
• W4387357363 creator A5087862105 @default.
• W4387357363 date "2023-10-05" @default.
• W4387357363 modified "2023-10-17" @default.
• W4387357363 title "The SET and ankyrin domains of the secreted <i>Legionella pneumophila</i> histone methyltransferase work together to modify host chromatin" @default.
• W4387357363 cites W1007961504 @default.
• W4387357363 cites W1178773072 @default.
• W4387357363 cites W145043445 @default.
• W4387357363 cites W1747289823 @default.
• W4387357363 cites W1947842818 @default.
• W4387357363 cites W1967841171 @default.
• W4387357363 cites W1977087875 @default.
• W4387357363 cites W1978358191 @default.
• W4387357363 cites W1990965195 @default.
• W4387357363 cites W1997600163 @default.
• W4387357363 cites W2004437771 @default.
• W4387357363 cites W2014278482 @default.
• W4387357363 cites W2031611770 @default.
• W4387357363 cites W2034102180 @default.
• W4387357363 cites W2034391603 @default.
• W4387357363 cites W2062270875 @default.
• W4387357363 cites W2065155413 @default.
• W4387357363 cites W2065434762 @default.
• W4387357363 cites W2066210800 @default.
• W4387357363 cites W2072052008 @default.
• W4387357363 cites W2075563069 @default.
• W4387357363 cites W2106473601 @default.
• W4387357363 cites W2110813417 @default.
• W4387357363 cites W2124026197 @default.
• W4387357363 cites W2124207075 @default.
• W4387357363 cites W2127092072 @default.
• W4387357363 cites W2130675249 @default.
• W4387357363 cites W2132926880 @default.
• W4387357363 cites W2133255279 @default.
• W4387357363 cites W2141452262 @default.
• W4387357363 cites W2157354730 @default.
• W4387357363 cites W2167279371 @default.
• W4387357363 cites W2180229411 @default.
• W4387357363 cites W2233407458 @default.
• W4387357363 cites W2309421679 @default.
• W4387357363 cites W2334542052 @default.
• W4387357363 cites W2607585298 @default.
• W4387357363 cites W2771040219 @default.
• W4387357363 cites W2795121612 @default.
• W4387357363 cites W2808507323 @default.
• W4387357363 cites W2970441159 @default.
• W4387357363 cites W2982322669 @default.
• W4387357363 cites W3011106749 @default.
• W4387357363 cites W3014409069 @default.
• W4387357363 cites W4212847052 @default.
• W4387357363 cites W4248872320 @default.
• W4387357363 cites W4292606943 @default.
• W4387357363 cites W4313307993 @default.
• W4387357363 cites W54756646 @default.
• W4387357363 doi "https://doi.org/10.1128/mbio.01655-23" @default.
• W4387357363 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37795993" @default.
• W4387357363 hasPublicationYear "2023" @default.
• W4387357363 type Work @default.
• W4387357363 citedByCount "0" @default.
• W4387357363 crossrefType "journal-article" @default.
• W4387357363 hasAuthorship W4387357363A5005759921 @default.
• W4387357363 hasAuthorship W4387357363A5029808456 @default.
• W4387357363 hasAuthorship W4387357363A5040472662 @default.
• W4387357363 hasAuthorship W4387357363A5049173678 @default.
• W4387357363 hasAuthorship W4387357363A5049223590 @default.
• W4387357363 hasAuthorship W4387357363A5075868129 @default.
• W4387357363 hasAuthorship W4387357363A5087862105 @default.
• W4387357363 hasBestOaLocation W43873573631 @default.
• W4387357363 hasConcept C104317684 @default.
• W4387357363 hasConcept C113241181 @default.
• W4387357363 hasConcept C150425827 @default.
• W4387357363 hasConcept C2776118409 @default.
• W4387357363 hasConcept C2776745794 @default.
• W4387357363 hasConcept C523546767 @default.
• W4387357363 hasConcept C54355233 @default.
• W4387357363 hasConcept C55493867 @default.
• W4387357363 hasConcept C64927066 @default.
• W4387357363 hasConcept C83640560 @default.
• W4387357363 hasConcept C86803240 @default.
• W4387357363 hasConcept C95444343 @default.
• W4387357363 hasConceptScore W4387357363C104317684 @default.
• W4387357363 hasConceptScore W4387357363C113241181 @default.
• W4387357363 hasConceptScore W4387357363C150425827 @default.
• W4387357363 hasConceptScore W4387357363C2776118409 @default.
• W4387357363 hasConceptScore W4387357363C2776745794 @default.
• W4387357363 hasConceptScore W4387357363C523546767 @default.
• W4387357363 hasConceptScore W4387357363C54355233 @default.
• W4387357363 hasConceptScore W4387357363C55493867 @default.
• W4387357363 hasConceptScore W4387357363C64927066 @default.
• W4387357363 hasConceptScore W4387357363C83640560 @default.
• W4387357363 hasConceptScore W4387357363C86803240 @default.
• W4387357363 hasConceptScore W4387357363C95444343 @default.
• W4387357363 hasFunder F4320320883 @default.

• next