Structure of the ribosome

Finally, to produce the structural and functional devices of the cell, polypeptides are synthesized by ribosomal translation of the mRNA. The supramolecular complex of the E. coli ribosome consists of 52 protein and three RNA molecules. The power of programmed molecular recognition is impressively demonstrated by the fact that aU of the individual 55 ribosomal building blocks spontaneously assemble to form the functional supramolecular complex by means of noncovalent interactions. The ribosome contains two subunits, the 308 subunit, with a molecular weight of about 930 kDa, and the 1590-kDa 50S subunit, forming particles of about 25-nm diameter. The resolution of the well-defined three-dimensional structure of the ribosome and the exact topographical constitution of its components are still under active investigation. Nevertheless, the localization of the multiple enzymatic domains, e.g., the peptidyl transferase, are well known, and thus the fundamental functions of the entire supramolecular machine is understood [24]. 

The structure of the ribosome s large subunit has recently been resolved at 2.4-A resolution by means of x-ray crystallography N Ban, P Nissen, J Hansen, PB Moore, TA Steitz. Science... 

The atomic structure of this subunit and its complexes with substrate analogs revealed the enzymatic activity of the rRNA backbone. Thus, the ribosome is in fact a ribozyme P Nissen, J Hansen, N Ban, PB Moore, TA Steitz. Science 289 920-930, 2000. Atomic structure of the ribosome s small 30S subunit, resolved at 5 A WM Clemons Jr, JL May, BT Wimberly, JP McCutcheon, MS Capel, V Ramakrishnan. Nature 400 833-840, 1999. The 8-A crystal structure of the 70S ribosome reveals a double-helical RNA bridge between the 50S and the 30S subunit GM Culver, JH Cate, GZ Yusupova, MM Yusupov, HF Noller. Science 285 2133-2136, 1999. 

The elucidation of the primary structure of the ribosomal proteins was very much facilitated by several improvements in the amino acidsequencing technique, especially on the micro scale. These resulted in... 

The new crystal structure of the ribosome—RFl complex sheds more light into the interactions between the GGQ motif and the peptidyltransferase center. This complex represents the product state of peptide release since a deacylated tRNA is bound to the P site. Importantly, the main chain amide of the conserved glutamine hydrogen bonds to the 3 OH of A76 in the P site, which is the leaving group of the hydrolysis... 

The structure of the ribosomal protein L9 from B. stearothermophilus is shown in Fig. 3. The folding kinetics and thermodynamics of its C-terminal domain have been studied as a function of pH by NMR and CD spectroscopies. The ionization state of the two histidines (Hisl06 and His 134) was found to be essential for the global stability and the folding rate of the protein. ... 

During the previous few years, the number of RNA crystal structures has increased in an exponential manner. This is mainly due to the fact that RNA is increasingly viewed as a predominant part of biological processes such as translation, ribozyme catalysis, and gene regulation (RNAi (Kamath et ah, 2003), riboswitches (Barrick et ah, 2004), and mRNA-protein interactions (Lescure et ah, 2002)), for which the gap in structural knowledge is still deep despite the determination of the crystal structure of the ribosome (Clemons et ah, 2001 Ban et ah, 2000 Yusupov et ah, 2001). 

Fig. 3 Secondary structure of the ribosomal rRNA of Saccharomyces cerevisiae. http //www.ma.icmb.utexas. edu (Cannone et al. 2002). The numbering of nucleotides is according to E. coli. Helices H) discussed in the text are highlighted and localization of yeast rdn mutations are indicated, a Secondary structure of the small subunit 18S rRNA. Helices discussed in the text are labeled in red. b Secondary structure of the 25 rRNA. Helices discussed in the text are labeled in blue. Helix 44 is part of the L7/L12 stalk hehx 95 contains the sarcin-ricin loop. For details, see text...

Yusupov MM, Yusupova GZ, Baucom A, Lieberman K, Earnest TN, Cate JH, Noller HF (2001) Crystal structure of the ribosome at 5.5A resolution. Science 292 883—896 Zhouravleva G, Frolova L, Le Goff X, Le Guellec R, Inge-Vechtomov S, Kisselev L, Philippe M (1995) Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRFl and eRF3. EMBO J 14 4065-4072... 

See for the latest example, http//nobelprize.org/nobel jirizes/chemistry/laureates/2009/, for a 25-year long struggle for the determination of the structure of the ribosome, involving heavy computational effort. 

An understanding of protein synthesis, the most complex biosynthetic process, has been one of the greatest challenges in biochemistry. Eukaryotic protein synthesis involves more than 70 different ribosomal proteins 20 or more enzymes to activate the amino acid precursors a dozen or more auxiliary enzymes and other protein factors for the initiation, elongation, and termination of polypeptides perhaps 100 additional enzymes for the final processing of different proteins and 40 or more kinds of transfer and ribosomal RNAs. Overall, almost 300 different macromolecules cooperate to synthesize polypeptides. Many of these macromolecules are organized into the complex three-dimensional structure of the ribosome. 

Every chapter fully updated Including coverage of the human genome and genomics integrated throughout, and key developments since the publication of the third edition, such as the structure of the ribosome. 

Includes a presentation and analysis of the long-awaited structure of the ribosome--one of the most important updates in this new edition... 

Ribosomal RNA Is an Integral Part of the Ribosome The Fine Structure of the Ribosome Is Beginning to Emerge... 

We considered the structure of the ribosome in some detail in the previous chapter without referring to those sites that are functionally important in protein synthesis. Here we can localize some of the functional sites on the two ribosomal subunits (fig. 29.6). The mRNA binds to the smaller ribosomal subunit. The peptidyl transferase is an integral part of the 50S subunit, and the elongation factor EF-G binds to the 50S subunit. The nascent polypeptide chain exits through a channel in the 50S subunit. Two functional sites occur on... 

Chapters 27. 28, and 29 cover DNA replication, recombination, and repair RNA synthesis and splicing and protein synthesis. Evolutionary connections between prokaryotic systems and eukaryotic systems reveal how the basic biochemical processes have been adapted to function in more-complex biological systems. The recently elucidated structure of the ribosome gives students a glimpse into a possible early RNA world, in which nucleic acids, rather than proteins, played almost all the major roles in catalyzing important pathways. 

Electron microscopic studies of the ribosome at increasingly high resolution provided views of the overall structure and revealed the positions of tRNA-binding sites. Astounding progress on the structure of the ribosome has been made by x-ray crystallographic methods, after the pioneering work by Ada Yonath. The structures of both the 30S and the 50S subunits have been determined at or close to atomic resolution, and the elucidation of the structure of intact 70S... 

A. Yonath and F. Franceschi. 1998. Funchonal universality and evoluhonary diversity Insights from the structure of the ribosome Structure 6 679-684. (PubMed)... 

Just a few months ago the structure of the ribosome (an BJSIA enzyme) was solved by parallel studies at several places, in Hamburg by the Max Planck group at DESY (Deutsches Elektronen Synchrotron) and at the Weizmann Institute in Israel, at Yale University, and in Cambridge, England. Three years before we had determined another complex structure, the proteasome, which was the most complex one to date at that time. More and more complex systems are being studied and the attribute most complex is... 

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. 

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