A covariation analysis reveals elements of selectivity in quorum sensing systems
| Autor: | Amy L. Schaefer, David Baker, Angelina Zimenko, Emily Kenna MacLeod, Qian Cong, Samantha Wellington Miranda, E. Peter Greenberg |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein Conformation
QH301-705.5 Systems biology Science Population Computational biology medicine.disease_cause protein coevolution General Biochemistry Genetics and Molecular Biology intercellular signaling 03 medical and health sciences 0302 clinical medicine Bacterial Proteins medicine Amino Acid Sequence Biology (General) education 030304 developmental biology Microbiology and Infectious Disease 0303 health sciences education.field_of_study Binding Sites General Immunology and Microbiology biology Host (biology) Pseudomonas aeruginosa General Neuroscience Quorum Sensing food and beverages Gene Expression Regulation Bacterial General Medicine biochemical phenomena metabolism and nutrition biology.organism_classification Quorum sensing Amino Acid Substitution Chemical signal LasR-LasI Medicine Other 030217 neurology & neurosurgery Bacteria Research Article Computational and Systems Biology |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| Popis: | Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand-binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated that covariation methods provide a powerful approach for investigating selectivity in protein-small molecule interactions and have deepened our understanding of how communication systems evolve and diversify. eLife digest Communication is vital in any community and it is no different for bacteria. Some of the microbes living in bacterial communities are closely related to one another and can help each other survive and grow. They do this by releasing chemical signals that coordinate their behaviors, including those that are damaging to the infected host. A key aspect of this coordination is knowing how many related bacteria are present in a given environment. In a process known as quorum sensing, the bacteria release a chemical signal which neighboring sibling bacteria detect and respond to. The larger the population of bacteria, the more the signal accumulates. At a certain threshold, the signal activates the genes needed to trigger a coordinated action, such as producing toxins or antibiotics. Many bacteria communicate using acylhomoserine lactone signaling systems, which involve different signals depending on the species of bacteria. But it is unclear how this diversity evolved, and how bacteria can distinguish between signals from related and unrelated bacterial cells. To understand this, Wellington Miranda et al. used computational techniques to analyze how the proteins responsible for acylhomoserine lactone signaling coevolved. The analysis identified specific parts of these proteins that determine which signal will be produced and which will trigger a bacterium into action. Wellington Miranda et al. then used these insights to engineer the bacteria Pseudomonas aeruginosa to produce and respond to a signal that is naturally made by another bacterial species. These computational methods could be used to analyze other proteins that have coevolved but do not physically interact. Within the area of quorum sensing, this approach will help to better understand the costs and benefits of signal selectivity. This may help to predict bacterial interactions and therefore behaviors during infections. |
| Databáze: | OpenAIRE |
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