New Study Reveals Proteins' Dynamic Shapes under Pressure and Heat

Proteins are known to change shape to perform functions like binding to metabolites or other proteins. Understanding these shape-shifts is crucial for disease prevention and treatment, yet current methods fall short in providing comprehensive insights into the intricate three-dimensional forms of proteins. In a new study, researchers at the Advanced Science Research Center at the CUNY Graduate Center (CUNY ASRC) conducted an experiment aiming to unveil distinct protein shapes through X-ray crystallography imaging under elevated temperature and pressure. The findings, detailed in Communications Biology, present help improve our understanding of protein dynamics.

"Protein structures don't sit still; they shift between several similar shapes much like a dancer," explains Daniel Keedy, the principal investigator of the study. “Unfortunately, existing approaches for viewing proteins only reveal one shape, or suggest the presence of multiple shapes without providing specific details. We wanted to see if different ways of poking at a protein could give a us a more detailed view of how it shape-shifts.”

The study focused on STEP (PTPN5), a drug target protein for diseases like Alzheimer's, subjected to agitation using high pressure (2,000 times Earth's atmospheric pressure) and high temperature (body temperature).

The X-ray crystallography results revealed that elevated temperature and pressure induced diverse effects on the protein, exposing distinct shapes. Although high pressure isn't a condition that proteins encounter in the body, the agitation method provided insights into different structural states relevant to the protein's activity in human cells.

“Having the ability to use perturbations such as heat and pressure to elucidate these different states could give drug developers tools for determining how they can trap a protein in a particular shape using a small-molecule drug to diminish its function,” Keedy adds.