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• W4225633063 abstract "During nutrient limitation, bacteria produce the alarmones (p)ppGpp as effectors of a stress signaling network termed the stringent response. RsgA, RbgA, Era, and HflX are four ribosome-associated GTPases (RA-GTPases) that bind to (p)ppGpp in Staphylococcus aureus. These enzymes are cofactors in ribosome assembly, where they cycle between the ON (GTP-bound) and OFF (GDP-bound) ribosome-associated states. Entry into the OFF state occurs upon hydrolysis of GTP, with GTPase activity increasing substantially upon ribosome association. When bound to (p)ppGpp, GTPase activity is inhibited, reducing 70S ribosome assembly and growth. Here, we determine how (p)ppGpp impacts RA-GTPase-ribosome interactions. We show that RA-GTPases preferentially bind to 5'-diphosphate-containing nucleotides GDP and ppGpp over GTP, which is likely exploited as a regulatory mechanism within the cell to shut down ribosome biogenesis during stress. Stopped-flow fluorescence and association assays reveal that when bound to (p)ppGpp, the association of RA-GTPases to ribosomal subunits is destabilized, both in vitro and within bacterial cells. Consistently, structural analysis of the ppGpp-bound RA-GTPase RsgA reveals an OFF-state conformation similar to the GDP-bound state, with the G2/switch I loop adopting a conformation incompatible with ribosome association. Altogether, we highlight (p)ppGpp-mediated inhibition of RA-GTPases as a major mechanism of stringent response-mediated ribosome assembly and growth control. IMPORTANCE The stringent response is a bacterial signaling network that utilizes the nucleotides pppGpp and ppGpp to reprogram cells in order to survive nutritional stresses. However, much about how these important nucleotides control cellular reprogramming is unknown. Our previous work revealed that (p)ppGpp can bind to and inhibit the enzymatic activity of four ribosome-associated GTPases (RA-GTPases), enzymes that facilitate maturation of the 50S and 30S ribosomal subunits. Here, we examine how this occurs mechanistically and demonstrate that this interaction prevents the accommodation of RA-GTPases on ribosomal subunits both in vitro and within bacterial cells, with the ppGpp-bound state structurally mimicking the inactive GDP-bound conformation of the enzyme. We additionally reveal that these GTPase enzymes have a greater affinity for OFF-state-inducing nucleotides, which is a mechanism likely to control ribosome assembly during growth. With this, we further our understanding of how ribosome function is controlled by (p)ppGpp, enabling bacterial survival during stress." @default.
• W4225633063 created "2022-05-05" @default.
• W4225633063 creator A5007097007 @default.
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• W4225633063 creator A5051040373 @default.
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• W4225633063 date "2021-12-21" @default.
• W4225633063 modified "2023-10-10" @default.
• W4225633063 title "The Stringent Response Inhibits 70S Ribosome Formation in <i>Staphylococcus aureus</i> by Impeding GTPase-Ribosome Interactions" @default.
• W4225633063 cites W1512441902 @default.
• W4225633063 cites W151679603 @default.
• W4225633063 cites W1528423270 @default.
• W4225633063 cites W1568532879 @default.
• W4225633063 cites W1578462326 @default.
• W4225633063 cites W1727342911 @default.
• W4225633063 cites W1928733522 @default.
• W4225633063 cites W1975139404 @default.
• W4225633063 cites W1990048403 @default.
• W4225633063 cites W1990503265 @default.
• W4225633063 cites W1992031613 @default.
• W4225633063 cites W1992191105 @default.
• W4225633063 cites W2000236507 @default.
• W4225633063 cites W2006922696 @default.
• W4225633063 cites W2011764543 @default.
• W4225633063 cites W2017203445 @default.
• W4225633063 cites W2026249269 @default.
• W4225633063 cites W2026828254 @default.
• W4225633063 cites W2035300685 @default.
• W4225633063 cites W2038840577 @default.
• W4225633063 cites W2040441524 @default.
• W4225633063 cites W2044952065 @default.
• W4225633063 cites W2045074917 @default.
• W4225633063 cites W2045778300 @default.
• W4225633063 cites W2046055395 @default.
• W4225633063 cites W2064482407 @default.
• W4225633063 cites W2065850381 @default.
• W4225633063 cites W2068375963 @default.
• W4225633063 cites W2069309738 @default.
• W4225633063 cites W2070873808 @default.
• W4225633063 cites W2072853789 @default.
• W4225633063 cites W2081912151 @default.
• W4225633063 cites W2085255531 @default.
• W4225633063 cites W2100234064 @default.
• W4225633063 cites W2102367832 @default.
• W4225633063 cites W2108921801 @default.
• W4225633063 cites W2109719123 @default.
• W4225633063 cites W2113545203 @default.
• W4225633063 cites W2115736484 @default.
• W4225633063 cites W2118260821 @default.
• W4225633063 cites W2119896573 @default.
• W4225633063 cites W2124026197 @default.
• W4225633063 cites W2127322768 @default.
• W4225633063 cites W2134589804 @default.
• W4225633063 cites W2144081223 @default.
• W4225633063 cites W2147438744 @default.
• W4225633063 cites W2148111565 @default.
• W4225633063 cites W2156571424 @default.
• W4225633063 cites W2163341755 @default.
• W4225633063 cites W2163922114 @default.
• W4225633063 cites W2171810840 @default.
• W4225633063 cites W2226150319 @default.
• W4225633063 cites W2298446567 @default.
• W4225633063 cites W2327011266 @default.
• W4225633063 cites W2374393069 @default.
• W4225633063 cites W2553338927 @default.
• W4225633063 cites W2559180185 @default.
• W4225633063 cites W2607287508 @default.
• W4225633063 cites W2613482209 @default.
• W4225633063 cites W2750727388 @default.
• W4225633063 cites W2752128520 @default.
• W4225633063 cites W2755679890 @default.
• W4225633063 cites W2765322245 @default.
• W4225633063 cites W2804822363 @default.
• W4225633063 cites W2809571448 @default.
• W4225633063 cites W2898103244 @default.
• W4225633063 cites W2904109453 @default.
• W4225633063 cites W2924755631 @default.
• W4225633063 cites W2936521062 @default.
• W4225633063 cites W2956102192 @default.
• W4225633063 cites W2958144560 @default.
• W4225633063 cites W2971098387 @default.
• W4225633063 cites W2980440799 @default.
• W4225633063 cites W3003369623 @default.
• W4225633063 cites W3012560802 @default.
• W4225633063 cites W3083008593 @default.
• W4225633063 cites W3091825627 @default.
• W4225633063 cites W3094868867 @default.
• W4225633063 cites W3119286080 @default.
• W4225633063 cites W3165323947 @default.
• W4225633063 cites W4234408276 @default.
• W4225633063 doi "https://doi.org/10.1128/mbio.02679-21" @default.
• W4225633063 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34749534" @default.
• W4225633063 hasPublicationYear "2021" @default.
• W4225633063 type Work @default.
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