Aminoacyl-tRNA synthases and ribosomal proofreading Flashcards
Where do the activation domain fragments of aaRS enzymes bind?
To opposite sides of tRNA acceptor stems
What do aaRS recognise on the tRNA?
tRNA acceptor stem plus anticodon
What happens to the aa-tRNA following the internal migration of the amino acid moiety?
The aa-tRNA takes part in peptide bond formation with the amino acid esterified to 3’-OH of terminal ribose regardless of initial attachment site
What part of the cognate amino acid do aaRS enzymes recognise?
The R groups
Some pairs of amino acids are so similar that what can happen?
They can be recognised by the ‘wrong’ aaRS
What is the overall error frequency of the activation and charging of an amino acid to cognate tRNA?
1 in 1.6 x 10^5
Is the first step of the activation and charging of an amino acid to cognate tRNA reversible or irreversible? Why?
First step is irreversible due to cleavage of PPi
What did Fersht propose?
tRNA selection by aaRS is much more accurate than amino acid selection
What does the ‘double sieve’ model for amino acid selection involve?
2 sites on aaRS:
- Acylation or activation site
- Hydrolytic or editing site
What does editing involve?
The co-substrate tRNA
If the amino acid on the swinging arm of tRNA fits into the editing site of aaRS what can happen?
It can be hydrolysed out
What is an acceptable error frequency?
Consider:
A protein with 300 amino acids
Error frequency 1 in 10^4
Only 3% of proteins affected
GTP hydrolysis (in either case) is what?
Proofreading at a cost
Stoichiometry of GTPase is a measure of what?
Proofreading
The ribosome has evolved to deliver what?
Optimal growth rate
Accuracy; need vs. cost
