Journal Article

Proofreading through spatial gradients

Husain, Kabir, Galstyan, Vahe, Xiao, Fangzhou, Phillips, Rob, Murugan, Arvind

2020

Overview

Key enzymatic processes use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. The applicability of traditional proofreading schemes, however, is limited because they typically require dedicated structural features in the enzyme, such as a nucleotide hydrolysis site or multiple intermediate conformations. Here, we explore an alternative conceptual mechanism that achieves error correction by having substrate binding and subsequent product formation occur at distinct physical locations. The time taken by the enzyme–substrate complex to diffuse from one location to another is leveraged to discard wrong substrates. This mechanism does not have the typical structural requirements, making it easier to overlook in experiments. We discuss how the length scales of molecular gradients dictate proofreading performance, and quantify the limitations imposed by realistic diffusion and reaction rates. Our work broadens the applicability of kinetic proofreading and sets the stage for studying spatial gradients as a possible route to specificity.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
• Subject: Biological products / Biophysical Phenomena / compartmentalization / diffusion / DNA Replication - physiology / energy expenditure / Enzymes / error correction / Hydrolysis / Kinetics / Models, Biological / molecular gradients / Physics of Living Systems / Protein Biosynthesis - physiology / Structural Biology and Molecular Biophysics / Substrate Specificity - physiology