Stages and mechanisms of translation, regulation of translation. Antibiotics – ingibitors of transcription and translation.

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Stages and mechanisms of translation, regulation of translation. Antibiotics – ingibitors of transcription and translation

STAGES OF TRANSLATION 1. Recognition 2. Initiation 3. Elongation 4. Termination

Aminoacyladenilate RECOGNITION Aminoacyl-tRNA-synthetase Aminoacyladenilate + tRNA  aminoacyl-tRNA + AMP

Activation of amino acids Each amino acid has a specific tRNA There is specific aminoacyl-tRNA-synthetase for each AA

The structure of tRNA

Initiation of Translation The translation complex is assembled at the beginning of the mRNA coding sequence Complex consists of: -Ribosomal subunits -mRNA template to be translated -Initiator tRNA molecule -Protein initiation factors

Initiator tRNA First codon translated is usually AUG The initiator tRNA recognizes initiation codons -Bacteria: N-formylmethionyl-tRNA -Eukaryotes: methionyl-tRNA

Initiation of protein biosynthesis Methionyl- тRNA binds to P- center

Sites for tRNA binding in ribosomes There are two centers: peptidyl (P) and aminoacyl (А)

Elongation 1) Positioning of the next aminoacyl-tRNA in the A site 2) Formation of the peptide bound (enzyme – peptidyl transferase) between methionine and AA in A- centre. The residue of methionine is transferred on the amino group of another AA 3) Translocation – shift of ribosome by one codon. Methionyl-tRNA is released from P-centre. Dipeptidyl- tRNA moves from A-centre to P-centre.

Termination of Translation Ribosome comes to terminal codon UGA, UAG or UAA No tRNA molecules recognize these codons and protein synthesis stalls Protein termination factors F-1, RF-2, RF-3 split off synthesized polypeptide from the last tRNA Ribosomal complex dissociates

Termina- tion of Trans- lation

POSTTRANSLATIONAL MODIFICATION 1)Preparing of proteins for different functions 2)Direction of proteins to different locations (targeting) 1.Removing of methionine (formylmethionine) 2.Formation of disulfide and other bonds (secondary, tertiary structures) 3. Proteolytic cleavage 4. Modification of amino acid residues: - Hydroxylation - Glycosilation - Phosphorilation 5. Joining of prosthetic groups or cofactors 6. Formation of the quaternary structure

Regulation of the Protein Biosynthesis The operon model (by Jacob and Monod)

Inhibitors of Transcription

Antibiotics inhibiting protein synthesis