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Following evolutionary paths to protein-protein interactions with high affinity and selectivity
- Source :
- Nature Structural & Molecular Biology. 16:1049-1055
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- How do intricate multi-residue features such as protein-protein interfaces evolve? To address this question, we evolved a new colicin-immunity binding interaction. We started with Im9, which inhibits its cognate DNase ColE9 at 10(-14) M affinity, and evolved it toward ColE7, which it inhibits promiscuously (Kd > 10(-8) M). Iterative rounds of random mutagenesis and selection toward higher affinity for ColE7, and selectivity (against ColE9 inhibition), led to an approximately 10(5)-fold increase in affinity and a 10(8)-fold increase in selectivity. Analysis of intermediates along the evolved variants revealed that changes in the binding configuration of the Im protein uncovered a latent set of interactions, thus providing the key to the rapid divergence of new Im7 variants. Overall, protein-protein interfaces seem to share the evolvability features of enzymes, that is, the exploitation of promiscuous interactions and alternative binding configurations via 'generalist' intermediates, and the key role of compensatory stabilizing mutations in facilitating the divergence of new functions.
- Subjects :
- Models, Molecular
inorganic chemicals
Molecular Conformation
Colicins
Biology
Protein–protein interaction
Evolution, Molecular
Structural Biology
Immunity
Protein Interaction Mapping
Hydrolase
Molecular Biology
Organism
Recombination, Genetic
Genetics
Microbial toxins
Deoxyribonucleases
technology, industry, and agriculture
Epistasis, Genetic
biochemical phenomena, metabolism, and nutrition
Evolvability
Kinetics
Phenotype
Mutagenesis
Colicin
Mutation
bacteria
lipids (amino acids, peptides, and proteins)
Systematic evolution of ligands by exponential enrichment
Protein Binding
Subjects
Details
- ISSN :
- 15459985 and 15459993
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Nature Structural & Molecular Biology
- Accession number :
- edsair.doi.dedup.....552ac6c4c43d4ef625a381bdc8b117c0