Analyzing dynamic proteins in cell membrane

Chemistry professor Mei Hong studies the structures of proteins embedded in cell membranes.

Analyzing dynamic proteins in cell membrane
“My lab’s goal is to really provide molecular insight, using NMR spectroscopy to answer a lot of structural, dynamic, and mechanistic questions” about membrane proteins, says Mei Hong, an MIT professor of chemistry. Photo: Ian MacLellan

The cell membrane is a biological membrane splits internal structure of all cells from the outside environment. It is in the form of a fluid, chaotic structures consist of fatty molecules. Producing analytical barriers between the cell and its surrounding, it contains some important proteins. The proteins make cells interact with outside environment. Such type of protein changes their structure when they are removed from membranes. Thus, it was difficult to analyze them. Mei Hong, an MIT professor of chemistry analyzed membranes and the proteins embedded in them. She studied dynamic proteins in the cell membrane by grasping intricacy.

She said, “You must be ready to spend time measuring under conditions where the signals are not very pretty, but it tells you a lot. Those dynamics are something that a lot of people don’t quite want to deal with. But it’s extremely important because so many drug targets are membrane proteins.”

Hong has developed a various novel technique that uses nuclear magnetic resonance (NMR) spectroscopy. That technique shows accurate information about the structure of these complicated proteins. Her aim is to provide molecular vision, using NMR spectroscopy to answer various, dynamic, and mechanistic questions.

Later, she used NMR to study how phospholipids. Phospholipids are major building blocks of membranes, take on their shapes. It contains fatty tails and protein heads. Fatty tails face internally and protein head faces externally. This research helps her to analyze dynamic proteins in cell membranes.

She said, “It did lay a lot of groundwork for thinking later on about membrane proteins. You need to know the lipid membrane environment, their conformation, dynamics, and the feel for it.”

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Some of the NMR technique allow her to understand the membrane structure of embedded in proteins and other biological molecules. NMR uses magnetic properties of atomic nuclei to show the structure of nuclei containing molecule. It also depends on labeling the proteins of interest with carbon-13 known as an isotope of carbon. Interactions between the carbon-13 atoms generate signals. These signals allow scientists to represent the proteins’ structure.

Earlier, NMR researchers marked only few carbon atoms per protein. This limits the information content of each measurement. Then Hong came up with a way to carefully mark more carbon atoms, but not so many. Because making the carbon-carbon interactions too many and difficult to interpret.

She also cultivates new method to measure how deeply a protein inserted into a membrane. This is for deciding the introducing a protein within a membrane, and to measure long distances between atoms of a protein.

Hong used this technique in the influenza M2 protein out of all proteins. The influenza M2 protein embedded in the membrane that forms the influenza viral envelope. The M2 protein also forms a proton channel. The influenza drugs amantadine and rimantadine interfere with M2 protein, preventing the virus from infecting host cells.

Hong said, “We did a lot of studies to figure out how drugs bind to it and what’s the drug-bound structure.”

Now she studying the structure and dynamics of virus fusion proteins, which are embedded in the viral envelope. This help viruses to fuse to the cells they are infecting.

“If you can inhibit these fusion proteins then you could stop the very first entry step, which makes them good drug targets,” she said.