Protein transformation gives new twist to medical research

Discovery in Texas has medical implications

It was a transforming moment. Researchers could barely believe their eyes. A molecular blob of a protein reshaped itself into a molecular Pacman in order to free new viruses from the inside of a bacterial cell. It’s the sort of thing where your graduate student tells you the results of an experiment and you say, ’You must have made a mistake,’ said Dr. Ryland Young, Texas Agricultural Experiment Station biochemist. But then, a good scientist has to be prepared at any time for the old rule to be disproved, he added.

And that’s what happens today when Science magazine reports on the protein Lyz found to be capable of turning itself into a completely different structure – a discovery made by Young’s graduate student Min Xu and a team of researchers.

Understanding Lyz could enable medical researchers to design drugs to turn off or on proteins at the cellular level, which could lead to treatment for some of the most difficult to cure diseases such as cancer and HIV.

Lyz is a lysozyme, a protein that degrades the tough cell wall that covers bacterial cells. The name lysozyme means break-out enzyme as coined by Alexander Fleming, who was also the inventor of penicillin. Lysozymes are everywhere, Young noted. They are even in your tears, where they destroy bacteria that try to enter the eye.

But Lyz is made by a virus growing inside the bacterial cell. The virus has to destroy the cell wall, or the virus babies would be trapped inside the dead body of the bacterium. Originally, the group set out to study how the Lyz protein gets outside the cell to break down the cell wall. They were looking for a holin, a protein that makes holes in the cell membrane to let the lysozyme out.

“Using biochemistry and genetics, Min and Doug (Struck, a research assistant) found something completely unexpected,” Young said. Lyz was able to get out of the membrane by presenting a part of the protein as a signal, or tether attached to the membrane. Once outside, Lyz completely changes its shape, withdrawing the signal from the membrane and turning into a jaw-like molecule that almost literally chews up the cell wall, thus allowing release of its progeny.

It’s like one of those transformer toys that you twist and they become something quite different from the original in shape and form, noted Sacchettini, whose group worked out the detailed molecular structure of Lyz before and after its shape-shifting. It’s fascinating to know now that the same protein can exist in vastly different states. It’s an academic exercise from which a lot of other interesting work and developments may derive.

Also working with Xu, Young, Sacchettini and Struck on the project were: Dr. Sam Arulandu, a post doctoral researcher, and undergraduate student Stephanie Swanson, a senior from Houston.