Designing bacterial signaling interactions with coevolutionary landscapes
| Autor: | Faruck Morcos, José N. Onuchic, Patricia A. Jennings, Ryan R. Cheng, Ellinor Haglund, Herbert Levine, Nicholas S. Tiee, Joseph A. Adams |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation lcsh:Medicine Bacillus Protein Sequencing medicine.disease_cause Pathology and Laboratory Medicine Biochemistry Database and Informatics Methods Protein sequencing Protein structure Medicine and Health Sciences lcsh:Science Mutation Multidisciplinary Escherichia coli Proteins Bacterial Pathogens Bacillus Subtilis Experimental Organism Systems Medical Microbiology Engineering and Technology Prokaryotic Models Directed Molecular Evolution Pathogens Sequence Analysis Bacterial Outer Membrane Proteins Signal Transduction Research Article Multiple Alignment Calculation Bioinformatics Sequence Databases Sequence alignment Computational biology Biology Research and Analysis Methods Microbiology Protein–protein interaction 03 medical and health sciences Multienzyme Complexes Computational Techniques medicine Escherichia coli Genetics Point Mutation Molecular Biology Techniques Sequencing Techniques Protein Interactions Microbial Pathogens Molecular Biology Bacteria Histidine kinase lcsh:R Organisms Biology and Life Sciences Proteins Protein engineering Split-Decomposition Method 030104 developmental biology Biological Databases Signal Processing lcsh:Q Sequence Alignment |
| Zdroj: | PLoS ONE, Vol 13, Iss 8, p e0201734 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Selecting amino acids to design novel protein-protein interactions that facilitate catalysis is a daunting challenge. We propose that a computational coevolutionary landscape based on sequence analysis alone offers a major advantage over expensive, time-consuming brute-force approaches currently employed. Our coevolutionary landscape allows prediction of single amino acid substitutions that produce functional interactions between non-cognate, interspecies signaling partners. In addition, it can also predict mutations that maintain segregation of signaling pathways across species. Specifically, predictions of phosphotransfer activity between the Escherichia coli histidine kinase EnvZ to the non-cognate receiver Spo0F from Bacillus subtilis were compiled. Twelve mutations designed to enhance, suppress, or have a neutral effect on kinase phosphotransfer activity to a non-cognate partner were selected. We experimentally tested the ability of the kinase to relay phosphate to the respective designed Spo0F receiver proteins against the theoretical predictions. Our key finding is that the coevolutionary landscape theory, with limited structural data, can significantly reduce the search-space for successful prediction of single amino acid substitutions that modulate phosphotransfer between the two-component His-Asp relay partners in a predicted fashion. This combined approach offers significant improvements over large-scale mutations studies currently used for protein engineering and design. |
| Databáze: | OpenAIRE |
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