Chapter 7- Kinetic proofreading and conformational proofreading Flashcards
What is robustness?
Special system designs that make biological systems able to fill their function despite natural noise.
It explains how biological systems can function in noisy environments.
What is the purpose of kinetic proofreading?
Achieving high precision in molecular interactions.
What is the genetic code?
The mapping between the 64 tRNA codons and the 20 amino acids.
What is the proofreading task that has to be solved in translation?
Wrong pairing between tRNA codons and mRNA anticodons (10^-4 mistakes)
What is the dissociation constant?
The ratio between the rate of diasociation and rate of asociation
K = k_dis / k_as
What is the most important constant when determining the error rate by binding affinities?
The off-rate constants of the correct and incorrect pairings (k_c and k_w).
How does the ribosome improve on the “simple” error rate calculations?
By having an extra step phosporylating the tRNA. This adds an extra discriminating step where the incorrect tRNA can fall off but not hop back on again.
What is the overall improvement of the error rate by the irreversibel kinetic proofreading?
(Kc/Kw)^n+1
where n is the number of irreversibel proofreading steps.
What is the overall concept of kinetic proofreading in the immune system?
Instead of relying on a irreversibel step, the immune system uses that the probability of dissociation over time (by performing non-equlibrium recptor phosphorylations) of the incorrect match is higher than that of the correct match.
What is the hallmark of kinetic proofreading?
A non-equilibrium reaction in the recognition process that forms an intermediary state providing a delay after binding. The system operates away from equilibrium -this means that ligands can’t circumvent the delay by just binding straight after.
What is induced fit?
Instead of the classical lock-and-key apporach to protrein binding, induced fit says that protein interaction happens by the protein adapting to the substrate.
What is the demand rule:
The binding site in the promotor is bound to its regulator most of the time.
When the regulator is bound expression less prone to errors.
The general concept of conformational proofreading:
Induced fit causes proteins to expend some energy bending. The probability of binding is equal to 1/(1+exp(deltaG)) - since delta-G is the sum of the bedning energy and the binding energy, the wrong matches has a higher binding energy and therefore seperation is created when the bending energy is added.
What are low expression genes regulated by?
Repressors - and high are activators.
