• mRNA
• tRNA
• ribosome
• factors
• protein

Advantage of the universality of the genetic code if you have a pt mutation at the third base in the codon triplet

chances are if you had a pt mutation at the 3rd postion, it likely will cause no effect

• c-myc- CUG
• bacteria- CUG, GUG

• you will get species specific preferential use of a specific codon set for an individual AA
• not all codons are used by a given organism
• the bias can shift during differentiation
• based on tRNA anticodon availability

• eukaryotic- UAA/UGA
• prokaryotic- UGA/UAG

• due to universality of genetic code
• you can have a limited number of tRNA's because the 3rd base does not impact the AA that is made, so the 3rd base is functioning only as a place holder
• tRNA may be able to read more the one codon without miscoding because it is the same AA

• position one is the most exposed and most flexible part of the structure, allow for wobbling
• the rest of the structure is very
• uniformity of rest of the molecule allow it to act with the ribosome in a very uniform fashion

Describe binding of aminoacyl-tRNA synthetase to tRNA

binds both acceptor stem and anticodon loop

• AA + ATP + tRNA + H2O → aminoacyl-tRNA + AMP + 2P

Rxn for initiation of translation to form fmet-tRNA

1. tRNA + Met
2. via synthetase, form methionyl-tRNA
3. formyl-tetrahydrofolate will add to methionyl-tRNA
4. forms fMet-tRNA

Role of IL-3

keeps 50S and 30S subunits dissociated

1. IL-2 complexed with GTP and fmet-tRNA
2. along with mRNA, the IL-2 complex binds with 30S subunit, leading to displacement of IL-3
   1. cause formation of initation complex stabilized by IL-1
3. initiation complex scan mRNA interaction with SD sequence and 16S rRNA
4. leads to strong interaction that place fmet-tRNA in AUG init. site
5. cause simultaneous binding for 50S subunit, causing GTP hydrolysis
6. hydrolysis leads to structural rearrangemented and dissociatiation of IF-1 and IF-2

• act as SD sequence for eukaryotes
• unlike prok, AUG start codon is part of the consensus sequence for binding of 43S complex

1. bring in AA-tRNA complexed with EF-Tu and GTP 
2. binding of specific AA-tRNA to A site, leads to GTP hydroylsis
3. peptide bond forms, leading to confirmation change that transfers from peptidyl tRNA to aminoacyl tRNA
4. transfer peptide chain from P site to A site
   1. ribosome moves one codon to the right, leading to the uncharged tRNA moving from P site to E site
5. repeat

Peptide bond formation in translation is catalyzed by what?

1. no tRNA to accommodate for term. triplet
2. competition for release factors
3. protein release factors fill in A site (struc. similar to tRNA)
4. cause hydrolysis of GTP, causing hydrolysis of peptide bond in P site with water
5. release of nascent polypeptide chain and protein release factor
6. binding of ribosome release factor to A site
7. GTP hydrolysis and dissociation of ribosomal subunits

Describe the phenomenon of post translational targeting

Describe the process "secretory" pathway/co-translational targeting for rER

1. signal sequence translated at 5' end of mRNA
2. recognition by signal recognition protein (SRP)
   1. further translation is temporarily halted
3. SRP recognizes docking protein on rER, leading to signal sequence being inserted into rER
4. SRP released
5. protein synthesis resumes, so polypeptide chain is pulled through membrane and signal sequence is cleaved off via signal peptidase in lumen of rER
6. ends with protein in lumen of rER and ribosome is recycled

1. secreted proteins enter ER as they are synthesized by ribosome
2. protein exit ER in vesicle
3. protein travel through cisternae of Golgi
4. exit via secretory vesicle
5. fuse with cell membrane, and spill contents

• when iron LOW/NOT PRESENT, ferratin binds to secondary structure on mRNA, blocking translation
• when high iron present, ferratin binds Fe and releases from mRNA, permitting translation

• when iron low, the Fe-S cluster in active site will dissociate and RNA molecules can bind in its place, stabilizting mRNA, so translation occurs
• when iron high, IRE in 3' untranslated region releases binding proteins, and destruction of transferrin receptor mRNA, so no translation

• transfer ADP-ribose uni from NAD to dipthiamide, a modified AA residue in EF 2
• leads to blocking EF-2, leading to blocking process of translocation

Toxins that inhibit EF via ADP ribosylation

pseudomonas toxin

diptheria toxin

• cholera- increase adenylyl cyclase which increase cAMP
• pertusis- membrane G protein signal

• three exons
• AUG start codon in secondy exon buried in a secondary stem loop structure between exon one and 2, leading to down regulation of translation
• CUG upstream of AUG that can serve as alternative start codon, altering function
• use IRES in exon 1 to avoid cap dependent initation of scanning (alter control and function)

• you lose exon 1, leading to no secondary structure to inhibit transcription
• lead to excess activation of myc expression

• IRE's in untranslated region
• IRE's bind to aconitase to stabilize structure WITHOUT effecting translation

Shigella dysenteriea

E coli enterotoxin

cator beans-ricin

1. Ricin heterodimer binds to ribosomal inactivation proteins
   1. beta chain of hetrodimer binds surface glycoprotein
   2. A chain depurinate 28S rRNA in highly conserved EF binding domain
   3. NO TRANSLATION

1. leads to exposed hydrophobic domains
2. two options
   1. aggregate, leading to diseased states
   2. ubiquitin tagged, leading to proteosome degredation