Climbing Up and Down Binding Landscapes through Deep Mutational Scanning of Three Homologous Protein–Protein Complexes
Michael Heyne, Jason Shirian, Itay Cohen, Yoav Peleg, Evette S. Radisky, Niv Papo, Julia M. Shifman
Abstract
values for the three PPIs, gleaned from tens of thousands of single and double mutations. We show that binding landscapes of the three complexes are strikingly different and depend on the PPI evolutionary optimality. We observe different patterns of couplings between mutations for the three PPIs with negative and positive epistasis appearing most frequently at hot-spot and cold-spot positions, respectively. The evolutionary trends observed here are likely to be universal to other biological complexes in the cell.
Topics & Concepts
EpistasisAffinitiesChemistryBinding affinitiesComputational biologyHomologous chromosomePlasma protein bindingGeneticsEvolutionary biologyBiochemistryGeneBiologyReceptorGenomics and Phylogenetic StudiesEvolution and Genetic DynamicsBioinformatics and Genomic Networks