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Page Title: Ribosome

Missing information:

In the section 'high resolution structure' X-ray crystallographic resolution of many ribosome structures have been mentioned and for the 50S prokaryotic ribosome structure characterised in 2000, the resolution is not mentioned, which is 2.4 and 3.3 angstroms, I believe it's important to have this information there as the Nobel prize was given for determining these structures.

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P-site

The P-site (for peptidyl) is the second binding site for t-RNA in the ribosome. The other two sites are the A-site (aminoacyl), which is the first binding site in the ribosome, and the E-site (exit), which is the third and final binding site in the ribosome. The P-site during translation holds the t-RNA which is linked to the growing polypeptide chain. When a stop codon is reached ending translation, the peptidyl-tRNA bond of the t-RNA located in the P-site is cleaved releasing the newly synthesized protein. During the translocation step of the elongation phase, the mRNA is advanced by one codon, coupled to movement of the tRNAs from the ribosomal A to P and P to E sites, catalyzed by elongation factor EF-G

Overview
The ribosomal P-site plays a vital role in all phases of translation. Initiation involves recognition of the start codon (AUG) by initiator tRNA in the P-site, elongation phase involves passage of many elongator tRNAs through the P site, termination phase involves hydrolysis of the mature polypeptide from tRNA bound to the P-site, and ribosome recycling involves release of deacylated tRNA.

Binding a tRNA to the P-site in the presence of mRNA establishes codon-anticodon interaction and this interaction is important for small subunit ribosome (30S) contacts to the tRNA.

Using Toeprinting assay, it has been shown that Protein Synthesis initiates from the A-site of the Ribosome in the cricket paralysis virus (CrPV). IGR-IRES (Intragenic regions-internal ribosome entry sites) can assemble 80S ribosomes from 40S and 60S ribosomal subunits in the absence of eIF2, Met-tRNAi, or GTP hydrolysis and without a coding triplet in the ribosomal P-site. Authors also showed IGR-IRES can direct translation of a protein whose N-terminal residue is not methionine.

Classical two-state model proposes that ribosome contains two binding sites for tRNA, P-site and A-site. The A-site binds to incoming to aminoacyl tRNA which has the anti-codon for the corresponding codon in the mRNA presented in the A-site. After peptide formation between the C-terminal carbonyl group of the growing polypeptide chain (attached to a P-site bound tRNA) and the amino group of the aminoacyl tRNA (A-site bound), the polypeptide chain is then attached to the tRNA in the A-site. The deacylated tRNA remains in the P-site and gets released once the peptidyl-tRNA is transferred to the P-site.

Using Chemical probing methods, a set of phylogenetically conserved bases in ribosomal RNA where the tRNA binds has been examined and suggested to be directly involved in the binding of tRNA to the ribosome. Correlation of such site specific protected bases in rRNA and occupancy of the A, P and E sites has allowed diagnostic assays of these bases to study the location of tRNA in any given state of the translational cycle. Authors proposed a hybrid model where higher affinity of the deactivated tRNA and peptide tRNA for the E and P sites of the 50S subunit, thermodynamically favour the P/P to P/E and A/A to A/P transitions.

Structure
The complete three dimensional structure of the T. thermophilus  70S ribosome was determined using X-ray crystallography, containing mRNA and tRNAs bound to the P and E sites at 5.5 Å resolution and to the A site at 7 Å resolution. Authors found that all three tRNA binding sites (A, P, and E) of the ribosome contact all three tRNAs at universally conserved parts of their structures; this allows the ribosome to bind different tRNA species in precisely the same way. The translocation step of protein synthesis inescapably requires movements of 20 Å or more by the tRNAs, as they move from the A to P to E sites.

tRNA Targeting Antibiotics
Oxazolidines (eg. linezolid) prevent the binding of the initiator tRNA at the P-site Oxazolidines have been demonstrated to pleiotropically affect initiator-tRNA binding, EF-P (elongation factor P) stimulated synthesis of peptide bonds, and EF-G-mediated translocation of initiator-tRNA into the P-site.

Macrolide, Lincosamide and Streptogramin class of antibiotics prevent peptide bond formation and/or the translocation of tRNA from the A-site to the P-site on the ribosome that eventually leads to interference with the elongation step and thus the inhibition of protein translation.