People, other animals, and plants have to appropriately respond to their environment in order to live. These responses start at the level of cells, and proteins that alter the membrane that surrounds cells or the membranes inside cells can change these responses. But how do proteins find the right membrane? Our research investigates how a particular class of proteins do this.
When released by disease-causing bacteria, this class of proteins can help hide the bacteria from responses that would kill them, while similar proteins in species such as plants can help keep the immune system from killing friendly bacteria that provide food. A detailed understanding of how these and other proteins find, bind to and alter membranes could help scientists fight disease and might help scientists design new proteins that find particular membranes and change the behavior of cells.
A detailed understanding of how these and other proteins find, bind to and alter membranes could help scientists fight disease.
I and my co-authors from Boston College and the University of Bergen reviewed decades of research on an important class of enzymes secreted by bacteria. This review article provides a paradigm for how to use a combined computational/experimental approach to study proteins that transiently interact with cell membranes altering how cells respond to the environment. It also provides a detailed molecular level view of how a class of enzymes from Gram positive bacteria (phosphatidylinositol-specific phospholipase Cs, associated with bacterial virulence) interact with cells, and helps explain how these enzymes are likely to help downregulate innate immunity in a variety of organisms promoting bacterial survival.
What happens next?
A combined experimental and computational toolkit can provide detailed, validated models for how membrane active enzymes transiently interact with cell membranes. For example, we have seen how protein-membrane interactions are modulated in different bacteria allowing these enzymes to help bacteria evade host immunity. This toolkit and these results should be useful to scientists studying how microbes associated with infectious diseases evade immunity and how the microbiome is tolerated by host organisms.