ABSTRACT
This chapter examines robustness to a fundamental source of errors in cells and considers kinetic proofreading in the immune system. Kinetic proofreading mimics the Picasso room by using nearly irreversible, nonequilibrium reactions as one-way doors. Kinetic proofreading is a general mechanism that provides specificity due to a delay step, which gives the incorrect ligands a chance to dissociate before recognition is complete. Advances by Gregoire Altan-Bonnet, Ronald Germain and Paul Francois show that specificity can be greatly improved by adding a negative feedback loop to kinetic proofreading. The hallmark of kinetic proofreading is a nonequilibrium reaction in the recognition process that forms an intermediate state, providing a delay after ligand binding. Conformational proofreading predicts the optimal degree of bending that maximizes specificity. The chapter shows that equilibrium binding can only provide discrimination that is as good as the ratio of the chemical affinity of the correct and incorrect targets.
