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21.
In the cell, the protein synthetic machinery is a highly complex apparatus that offers many potential sites for functional interference and therefore represents a major target for antibiotics. The recent plethora of crystal structures of ribosomal subunits in complex with various antibiotics has provided unparalleled insight into their mode of interaction and inhibition. However, differences in the conformation, orientation and position of some of these drugs bound to ribosomal subunits of Deinococcus radiodurans (D50S) compared to Haloarcula marismortui (H50S) have raised questions regarding the species specificity of binding. Revisiting the structural data for the bacterial D50S-antibiotic complexes reveals that the mode of binding of the macrolides, ketolides, streptogramins and lincosamides is generally similar to that observed in the archaeal H50S structures. However, small discrepancies are observed, predominantly resulting from species-specific differences in the ribosomal proteins and rRNA constituting the drug-binding sites. Understanding how these small alterations at the binding site influence interaction with the drug will be essential for rational design of more potent inhibitors. 相似文献
22.
Shpanchenko OV Zvereva MI Ivanov PV Bugaeva EY Rozov AS Bogdanov AA Kalkum M Isaksson LA Nierhaus KH Dontsova OA 《The Journal of biological chemistry》2005,280(18):18368-18374
tmRNA (transfer messenger RNA) is a unique molecule used by all bacteria to rescue stalled ribosomes and to mark unfinished peptides with a specific degradation signal. tmRNA is recruited by arrested ribosomes in which it facilitates the translational switch from cellular mRNA to the mRNA part of tmRNA. Small protein B (SmpB) is a key partner for the trans-translation activity of tmRNA both in vivo and in vitro. It was shown that SmpB acts at the initiation step of the trans-translation process by facilitating tmRNA aminoacylation and binding to the ribosome. Little is known about the subsequent steps of trans-translation. Here we demonstrated the first example of an investigation of tmRNA.ribosome complexes at different stages of trans-translation. Our results show that the structural element at the position of tmRNA pseudoknot 3 remains intact during the translation of the mRNA module of tmRNA and that it is localized on the surface of the ribosome. At least one SmpB molecule remains bound to a ribosome.tmRNA complex isolated from the cell when translation is blocked at different positions within the mRNA part of tmRNA. 相似文献
23.
Dandan Zhang Guangqiao Liu Jiaying Xue Jizhong Lou Knud H. Nierhaus Weimin Gong Yan Qin 《Nucleic acids research》2012,40(21):10851-10865
Translational GTPases (trGTPases) regulate all phases of protein synthesis. An early event in the interaction of a trGTPase with the ribosome is the contact of the G-domain with the C-terminal domain (CTD) of ribosomal protein L12 (L12-CTD) and subsequently interacts with the N-terminal domain of L11 (L11-NTD). However, the structural and functional relationships between L12-CTD and L11-NTD remain unclear. Here, we performed mutagenesis, biochemical and structural studies to identify the interactions between L11-NTD and L12-CTD. Mutagenesis of conserved residues in the interaction site revealed their role in the docking of trGTPases. During docking, loop62 of L11-NTD protrudes into a cleft in L12-CTD, leading to an open conformation of this domain and exposure of hydrophobic core. This unfavorable situation for L12-CTD stability is resolved by a chaperone-like activity of the contacting G-domain. Our results suggest that all trGTPases—regardless of their different specific functions—use a common mechanism for stabilizing the L11-NTD•L12-CTD interactions. 相似文献
24.
25.
R Häuser M Pech J Kijek H Yamamoto B Titz F Naeve A Tovchigrechko K Yamamoto W Szaflarski N Takeuchi T Stellberger ME Diefenbacher KH Nierhaus P Uetz 《PLoS genetics》2012,8(7):e1002815
The YbeB (DUF143) family of uncharacterized proteins is encoded by almost all bacterial and eukaryotic genomes but not archaea. While they have been shown to be associated with ribosomes, their molecular function remains unclear. Here we show that YbeB is a ribosomal silencing factor (RsfA) in the stationary growth phase and during the transition from rich to poor media. A knock-out of the rsfA gene shows two strong phenotypes: (i) the viability of the mutant cells are sharply impaired during stationary phase (as shown by viability competition assays), and (ii) during transition from rich to poor media the mutant cells adapt slowly and show a growth block of more than 10 hours (as shown by growth competition assays). RsfA silences translation by binding to the L14 protein of the large ribosomal subunit and, as a consequence, impairs subunit joining (as shown by molecular modeling, reporter gene analysis, in vitro translation assays, and sucrose gradient analysis). This particular interaction is conserved in all species tested, including Escherichia coli, Treponema pallidum, Streptococcus pneumoniae, Synechocystis PCC 6803, as well as human mitochondria and maize chloroplasts (as demonstrated by yeast two-hybrid tests, pull-downs, and mutagenesis). RsfA is unrelated to the eukaryotic ribosomal anti-association/60S-assembly factor eIF6, which also binds to L14, and is the first such factor in bacteria and organelles. RsfA helps cells to adapt to slow-growth/stationary phase conditions by down-regulating protein synthesis, one of the most energy-consuming processes in both bacterial and eukaryotic cells. 相似文献
26.
Incubation of 50 S subunits with 4.2 M LiCl leads to 4.2c cores and the complementary split protein fraction SP4.2, the latter containing quantitatively L24. L24 was removed from the split fraction by means of CM-cellulose chromatography. Partial and total reconstitution experiments performed with this protein preparation in the absence and presence of L24 demonstrate the crucial role of L24 in the early stage of assembly. However, this protein is dispensable for the subsequent steps of the in vitro assembly. 50 S subunits lacking L24 are fully active in the translation of artificial (poly(U)) and natural (R17 RNA) mRNA, indicating that L24 is not involved in any function of protein synthesis of the mature ribosome. It is therefore a mere assembly protein. 相似文献
27.
Preparation procedures of proteins and RNA influence the total reconstitution of 50S subunits from E. coli ribosomes. 总被引:1,自引:0,他引:1
A two-step procedure has been described for the total reconstitution of 50S ribosomal subunit from E. coli. RNA and proteins are mixed with stoichiometry of 1:1.2 and incubated at 44 degrees C in 4.0 mM Mg2+ followed by a second incubation at 50 degrees C in 20 mM Mg2+ (Dohme and Nierhaus, J. Mol. Biol. 107, 585 (1976)). A modified method recently reported makes use of an altered preparation technique for the RNA and proteins and requires an RNA to protein stoichiometry of 1:2.5 and 7.5 mM Mg2+ in the first incubation (Amils et al., Nucl. Acid Res. 5, 2455 (1978)). The latter requirements are not compatible with the findings obtained with the first procedure. A comparison of the various RNA and protein fractions from the different groups revealed that the Mg2+ dependence of reconstitution is a function of the RNA preparation, whereas the stoichiometry depends upon the technique used for isolation of the protein fraction. The different RNA preparations were compared in the electron microscope. 相似文献
28.
The (minus L15) character from the Escherichia coli strain AM16.98 was transduced to an RNase-deficient strain in order to enable a reconstitution analysis. The following results were obtained. 1) The strain lacking L15 showed a 2-3-fold prolonged generation time and the 70 S ribosomes a reduced tendency toward dissociation. 2) Active particles could not be reconstituted unless L15 was added. Addition of L15 regained activity, even if L15 was added after the two-step procedure during a third incubation. However, a modification of the standard two-step reconstitution procedure (lowering NH4+ from 400 to 240 mM and the incubation temperature of the second step from 50 to 47 degrees C) yielded 100% active particles in the absence of L15. Active particles could be formed which even lacked L15, L16, and L30. Addition of either L15 or L16 accelerated the formation of active particles in the second step by a factor of five, and both proteins together by a factor of more than 20. 3) The activation energy of the rate-limiting step of the second incubation was surprisingly reduced for about 20 kcal/mol in the absence of L15, although the corresponding rates were two to five times slower. We conclude 1) that L15 and L16 are late assembly proteins which accelerate the formation of active particles during the late assembly but are neither needed for the early assembly nor essential for ribosomal functions; 2) that some routes of the late assembly (e.g. incorporation of L16) are changing their significance depending on the NH4+ concentration and the absence and presence of L15; and 3) that different reactions are rate limiting during the second step incubation in the presence and absence of L15, respectively, and that the corresponding reaction rates exhibit a different temperature dependence. 相似文献
29.