Pervasive degeneracy and epistasis in a protein-protein interface

Abstract

Exploring the limits of protein sequence space Exploring the variability of individual functional proteins is complicated by the vast number of combinations of possible amino acid sequences. Podgornaia and Laub take on this challenge by analyzing four amino acids critical for the interaction between two signaling proteins in Escherichia coli. They build all the possible 160,000 variants of one of the two proteins and find that over 1650 are functional. Even though there can be very high variability in the composition of the interface between the two proteins, there are nonetheless strong context-dependent constraints for some amino acids, which suggests why many functional variants are not seen in nature. Science , this issue p. 673