As anyone who has ever worked in a group setting knows—communication is key. This concept holds true at the cellular level where different types of compounds must work together to carry out essential biological tasks. Findings published today in Proceedings of the National Academy of Sciences shed light on the communication method lipids use to talk to each other when they interact with membrane proteins, a primary target for drug discovery and potential treatment for a number of diseases.
The chemically complex environment of lipid membranes has made investigations into membrane signaling particularly difficult. For the current study, chemists at Texas A&M used native ion mobility mass spectrometry to monitor binding events at an ammonium channel of Escherichia coli and “see” membrane proteins as they interact with lipids.
They discovered compelling evidence that membrane proteins are capable of recruiting their own lipid microenvironments through allosteric regulation. In lipid-membrane interactions, it appears allostery allows proteins to alter their remote binding sites to accept lipids of different types. This knowledge could be leveraged for creation of novel pharmaceutical compounds and delivery methods.
"From this work and our previous work, it is becoming increasingly clear that membrane proteins are exquisitely sensitive to the chemistry of the lipid," says Texas A&M chemist Dr. Arthur Laganowsky's. "Given that lipid composition differs throughout the organs of the body, understanding how the lipid environment in these areas influences protein structure will be critical to opening new possibilities for pharmaceutical drugs designed to affect how these lipids bind with one another."
Image: Membrane protein samples are infused into the mass spectrometry using nanoflow electrospray ionization (nESI). In this artwork, free and lipid bound membrane proteins are emerging from droplets in the nESI process prior to entering the mass spectrometer. Image courtesy of the Laganowsky Laboratory, Texas A&M University.