Structure of Bacterial Ribosomes

Structure of Bacterial Ribosomes Roger A. Garrett and H. G. Wittmann... 

The study of protein synthesis offers another important reward a look at a world of RNA catalysts that may have existed before the dawn of life as we know it. Researchers have elucidated the structure of bacterial ribosomes, revealing the workings of cellular protein synthesis in beautiful molecular detail. And what did they find Proteins are synthesized by a gigantic RNA enzyme ... 

The dawn of a new millennium brought with it the elucidation of the first high-resolution structures of bacterial ribosomal subunits. The bacterial ribosome is complex, with a combined molecular weight of 2.7 million, and it is providing a wealth of surprises (Fig. 27-9). First, the traditional focus on the protein components of ribo-... 

The reconstitution of bacterial ribosomal subunits from the separated rRNAs and proteins, first announced in 1968, provides a potent tool to investigate such essential aspects of ribosome structure and evolution as the subunits assembly pathway [92,93], the locations and neighbourhoods of the subunit proteins [94,95], the roles of the individual proteins in both assembly and function [92,93,96], and the degree of exchangeability of ribosomal components both within and across domain boundaries [97,98]. 

A great deal of work is currently underway in many laboratories on the structure and function of the archaeal ribosome. These data, coupled with equivalent data forthcoming from the bacterial and eucaryal ribosomes, should answer many of the questions raised in this chapter. Of special interest will be the information obtained on the three-dimensional structure of the ribosome in the three domains. 

The sequences of the small and large rRNAs from several thousand organisms are now known. Although the primary nucleotide sequences of these rRNAs vary considerably, the same parts of each type of rRNA theoretically can form base-paired stem-loops, which would generate a similar three-dimensional structure for each rRNA in all organisms. The actual three-dimensional structures of bacterial rRNAs from Thermus thermopolis recently have been determined by x-ray crystallography of the 70S ribosome. The multiple, much smaller ribosomal proteins for the most part are associated... 

Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. Although clindamycin, erythromycin, and chloramphenicol are not structurally related, they act at sites in close proximity, and binding by one of these antibiotics to the ribosome may inhibit the interaction of the others. There are no clinical indications for the concurrent use of these antibiotics. Macrolide resistance due to ribosomal methylation by encoded enzymes also may produce resistance to clindamycin. However, because cUndamycin does not induce the methylase, there is cross-resistance only if the enzyme is produced con-stitutively. Clindamycin is not a substrate for macrolide efflux pumps thus, strains that are resistant to macrolides by this mechanism are susceptible to clindamycin. Altered metabolism occasionally causes clindamycin resistance. 

The first crystals of bacterial ribosomes in a three-dimensional lattice suitable for study by X-ray diffraction at a resolution of 1 nm were obtained by Yonath in about 1980. Now atomic structures are being established at a resolution of 0.3-0.1 nm, or less. s However, such progress would have been impossible without information about ribosomes obtained from improved cryo-electron micro-... 

Since much more is known about the structure and function of bacterial ribosomes, in particular those from Escherichia coli, than about those from eukaryotes, the following discussion will mainly deal with E. coli ribosomes. In the last chapter a comparison will be made between E. coli ribosomes and those of other organisms. 

FIGURE 11 Bacterial ribosome structure at 7.8 A. Architectural features of Thermus thermophilus 70S ribosomes are labeled, as identified by X-ray crystallography. The 308 subunit is the front, darker portion, and consists of the head (H) connected to the platform (P) and body (B). Other features of the 308 subunit are the neck (N), spur (8P), shoulder (8), and contacts between the head and platform (a and b). The 508 subunit includes the protein LI stalk, central protuberance (CP), and L7/L12 region. [Reprinted with permission from Cate, J. A., Yusupov, M. M., Yusupova, G. Zh., Earnest, T. N., and Noller, H. F. (1999). X-ray crystal structures of 708 ribosome functional complexes. Science 285, 2095-2104. 1999 American Association for the Advancement of 8cience.l... 

Not all the cellular DNA is in the nucleus some is found in the mitochondria. In addition, mitochondria contain RNA as well as several enzymes used for protein synthesis. Interestingly, mitochond-rial RNA and DNA bear a closer resemblance to the nucleic acid of bacterial cells than they do to animal cells. For example, the rather small DNA molecule of the mitochondrion is circular and does not form nucleosomes. Its information is contained in approximately 16,500 nucleotides that func-tion in the synthesis of two ribosomal and 22 transfer RNAs (tRNAs). In addition, mitochondrial DNA codes for the synthesis of 13 proteins, all components of the respiratory chain and the oxidative phosphorylation system. Still, mitochondrial DNA does not contain sufficient information for the synthesis of all mitochondrial proteins most are coded by nuclear genes. Most mitochondrial proteins are synthesized in the cytosol from nuclear-derived messenger RNAs (mRNAs) and then transported into the mito-chondria, where they contribute to both the structural and the functional elements of this organelle. Because mitochondria are inherited cytoplasmically, an individual does not necessarily receive mitochondrial nucleic acid equally from each parent. In fact, mito-chondria are inherited maternally. 

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