Ser Ser Ser. Tyr. Tyr. Stop Stop. Pro His Gln Arg. His. Pro. Pro. Gln. Asn. Ser Ser Arg Arg Val. Thr. Thr Thr Thr. Asn. Lys Lys. Asp Asp Glu Glu.

Transcription

1

2 he ly la Val Ile Trp Tyr Thr ys ro His ln rg he Tyr Stop Stop Stop ys ro ro ro His ln rg rg rg Ile Ile Met Thr Thr Thr sn sn Lys Lys rg rg Val Val Val la la la sp sp lu lu ly ly ly First osition (5 end) Second osition Third osition (3 end)

3 5 5 5

4 he ly la Val Ile Trp Tyr Thr ys ro His ln rg he Tyr Stop Stop Stop ys ro ro ro His ln rg rg rg Ile Ile Met Thr Thr Thr sn sn Lys Lys rg rg Val Val Val la la la sp sp lu lu ly ly ly First osition (5 end) Second osition Third osition (3 end)

5 he ly la Val Ile(Met) Trp Tyr Thr ys ro His ln rg he Tyr Stop Stop Stop(Trp) ys ro ro ro His ln rg rg rg Ile Ile Met Thr Thr Thr sn sn Lys Lys rg(stop) rg(stop) Val Val Val la la la sp sp lu lu ly ly ly First osition (5 end) Second osition Third osition (3 end)

6 he ly la Val Ile Trp Tyr Thr ys ro His ln rg he Tyr Stop Stop Stop ys ro ro ro His ln rg rg rg Ile Ile Met Thr Thr Thr sn sn Lys Lys rg rg Val Val Val la la la sp sp lu lu ly ly ly First osition (5 end) Second osition Third osition (3 end)

7

8

9 5 osition of nticodon Wobble osition I 3 osition of odon or or or or

10 R NH 3 H + H 2 denine H H yrophosphate denine H R NH 3 H H 2 H denine H denine H H 2 H H 2 H class I aminoacyl-trn synthetases class II aminoacyl-trn synthetases denine H 2 H NH 2 R H denine H 2 H NH 2 R H Transesterification atalytic?? Spontaneous??

11 monomeric or homodimeric minor groove 5 stranded parallel β sheet (Rossman Fold) anticodon, 3D structure, modified bases, base sequence on acceptor stem amino acid to 2 -H group rg, ys, ln, lu, Ile,, Met, Trp, Tyr, & Val identical dimer or two pairs of dimers major grove seven β strands connected by three α helices 3D structure, modified bases, base sequence on acceptor stem amino acid to 3 -H group la, sn, sp, ly, His, Lys, he, ro,, & Thr

12 N10-formyltetrahydrofolate tetrahydrofolate

13 Bacterial

14

15 IF-3 1 IF-1 IF-3 IF T IF IF-2 + T 5a + IF-3 IF T IF-2 IF-2 IF-3 1 5b D + IF-1

16 T D D EF-Tu EF-Ts T EF-Tu + T EF-Tu E T EF-Tu E E & D EF- T D E D EF- T EF- E 4 E T EF- E

17 NH 3 H 3 H 2 H 3 S H 2 S NH 3 H 2 H 2 H 2 H 2 H 2 H H 2 H 2 H 2 H 3 N N H H 3 N H H 2 H H 3 N H 2 H H

18 T D D EF-Tu EF-Ts T EF-Tu + T EF-Tu E T EF-Tu E E & D EF- T D E D EF- T EF- E 4 E T EF- E

19 T E E E + T or RF-3 T RF-1 RF-2 RRF D D T E E E D

20 eif2 D T eif2b eif2 T D eif2b (2) D T eif2 D T eif2b D eif2b eif2 T (3) eif2 T

21 eif6 eif6

22 eif3 eif1 eif1 eif3 eif1 eif1 eif2 T eif3 eif1 eif1 eif2 T

23 eif4e 5 eif4e eif4e eif4 eif4 eif4 mrn eif eif4 eif4

24 5 eif4b eif4e eif4b eif4 eif4 eif4h ab1 ab1 eif4h

25 eif1 eif1 43S reinitiation omplex eif3 eif4e eif1 eif4 eif2 T eif1 eif2 T 5 5 eif4b eif3 eif4e eif4 eif4b eif5 eif4 eif4h eif4 eif4h ab1 ab eif eif4-eif4e-eif4eif4b-eif4h-mrn omplex

26 5 5 eif4e eif4b T eif5b eif1 eif3 eif eif1 eif2 T eif5 eif4 eif4h ab1 T Hydrolysis stimulated by Start odon bound to Met-tRNi Met & eif5 Large Subunit

27 5 T Hydrolysis Expulsion of eif5b & eif6 Joining of Ribosomal Subunits

28 Elongation EF-Tu trn Binding & Locking eef1α EF-Ts NSINE NLETIDE- EXHNE FTR eef1βγ EF- Translocation eef2 Termination RF1 or RF2 Stop odon Recognition erf1 RF3 Ribosomal Recycling Factor with EF- & IF-3 DISSITES THER RELESE FTRS erf3 Dissociates Ribosome?

29 Tadpole alaxy rp 188

30 ontrol of Translation in Eukaryotes hosphorylation of S6 (small ribosomal subunit protein 6) shifts the ribosomes from inactive to active polysomes eif4f, the cap binding complex, is activated eif2 when phosphorylated binds eif2b tightly and the T for D exchange rxn inhibited eif2b and eif3 actions inhibited Inhibitory proteins bind to 3 untranslated end & poly tail inhibiting initiation eif4e Binding roteins (4E-B) inhibit the interaction between eif4e and eif4. eif4e Binding roteins inactivated by phosphorylation ene Silencing by RN Interference (RNi) RNi base pairs with the 3 untranslated end of the message to inhibit translation or stimulate mrn degradation RNi plays a role in the developmental timing in many organisms, often termed small temporal RN, strn

31 Inhibitors of Translation (Xenobiotics, ntibiotics, & Toxins) Streptomycin inhibits initiation in bacteria and causes misreading of the mrn. hloramphenicol binds to the 50S subunit and inhibits eptidyl Transferase. Tetracycline binds to the 30S subunit and inhibits trn binding to the ribosome. Erythromycin binds to the 50S subunit and inhibits eptidyl Transferase. ycloheximide inhibits translocation of peptidyl-trn in eukaryotes. It is used as an antivirus and a cancer chemotherapeutic agent. uromycin is an aminoacyl-trn analog which acts as a peptidyl acceptor stopping further peptide elongation. It is toxic to bacterial and eukaryotic cells. Diphtheria Toxin inactivates eef2. Ricin isolated from the castor bean (Ricinus communis) catalytically inactivates the 28S rrn of eukaryotic ribosomes.

32 otranslational & osttranslational Modifications rotein Targeting & Signal Sequence Removal mino Terminal Modifications Met Removal +, mino Terminal cetylation mino cid Modifications hosphorylation, Sulfation, arboxylation, Hydroxylation lycosylation ddition of Isoprenyl roups ddition of rosthetic roups Folding & Disulfide Bond Formation via xidation

33 Signal sequence T Signal Recognition article (SR) T D SR Receptor TRM T T T D D Sec61 eptide Translocation omplex (Translocon) Signal eptidase

34 Dolichol phosphate H 2 H 2 H 3 H2 H H 3 H 2 H2 H H 2 H H 3 H 3 n = 9 to 22 n

35 5 D D D D D D D M D D D D D D 4 D N-cetylglucosamine D D D 3 D Manose lucose