Pomona College Chemistry Professor Roberto Garza-López and his research colleagues have developed a new model that studies how protein molecules fold and unfold, work that has more than a few national institutes interested in the implications for understanding the development of diseases such as Alzheimer’s disease, Huntington’s disease, Type II diabetes and certain types of cancer, among others.

The research, recently published in the Journal of Inorganic Biochemistry, looked at the protein called Cytochrome c, and focuses on the question of what happens to this protein’s molecules when they don’t fold properly and how this improper unfolding is linked to cancers and other diseases.

So why does a protein fold and unfold in the first place? Long protein molecules start straight, explains Garza-López, but in order to interact with other molecules in the cell, they have to fold and go from one place in the cell to another. “For these long molecules to do anything positive, they have to first fold, and they have to fold in a very specific shape,” he says.

“If they don’t fold properly, then that’s where negative things occur, especially disease. In the paper we published, we are looking at the opposite effect: we’re looking at the protein that is already folded to see how it unfolds.”

The Howard Hughes Medical Institute (HHMI) and the National Institutes of Health (NIH) are providing grant money to the project for further research and are interested in what the team’s findings reveal about the early development of diseases. Garza-López is working with Caltech Professor Harry B. Gray and DePaul University Professor John J. Kozak.

“If you consider for example, a regular tape cassette: in a cassette player, the tape is arranged in a certain form, and that tape contains information, the same happens in this protein molecule. As the tape plays, it is decoded by the cassette player, this happens with proteins that are decoded within our cells and that decoded information can be nice music or nice sounds, but if not properly arranged, if something happens to the tape, the product will be something different.”  

That’s what happens when things go wrong in the molecule, he says.

Cytochrome c graphic created by Professor Roberto Garza-López

Cytochrome c graphic created by Professor Roberto Garza-López

In order to visualize the protein molecule’s many folds, students working in Garza-López’s lab get a chance to create 3-D structures of some of the proteins, like Cytochrome c (pictured here). The students’ 3-D graphics were also published in the recent article. 

“Students are very good with computers, at visualizing molecules and doing calculations, but they’re also very good at visualizing what those calculations are doing to those molecules.”

Sabari Kumar ‘17, a chemistry major who is working in Garza-López’s lab, was acknowledged in the published paper and is now studying, as a project of his senior thesis, the folding and unfolding of proteins related to disease by performing molecular dynamics simulations.

Another benefit of this research, says Garza-López who is also a faculty participant in the Pomona College Academy for Youth Success (PAYS) program, is that students at different stages can contribute, including his PAYS students. “They learn how to make these graphics, take information from the protein data bank to create these 3-D graphics.”

The research by Garza-López , Gray and Kozak continues, and they’re already finished with another manuscript looking at another protein called Intelectin-1, a protein of the intestines and lungs that is able to distinguish between human cells and the cells of bacterial invaders. 

“This could underpin new strategies to fight infections,” says Garza-López. “I knew we could study the folding/unfolding of this protein using our methodology.”

“Proteins are very complex.  We start with a simple model and we do a lot with that model and try to understand new things about it. That’s how science works.”