for the Prevention of Human Diseases
Rowen J.-Y. Chang, Ph.D
Professor of Molecular Medicine
The Center’s Focus
Functional proteins adopt defined three dimensional structures (native proteins) and acquire their native structures through a dynamic process that is encoded within their amino acid sequences (protein folding).
The focus of the Center is to determine the mechanism of protein folding and the reversed process (protein unfolding or protein denaturation). Elucidation of the mechanism of protein folding is essential to our understanding of how functional proteins are created and stabilized.
On the other hand, active proteins may unfold and change their shape under stressful environmental conditions. This denaturation process inactivates proteins, alters their metabolic pathway, and has been linked to the underlying mechanism that causes a number of neuro-degenerative diseases.
Understanding the mechanism of protein folding and unfolding represents currently one of the most challenging and important subjects in the field of protein chemistry. It is also crucial to our ultimate goal of designing new proteins with novel functions.
One major project of the Center is to elucidate the folding pathway of disulfide containing proteins. The laboratory is studying the folding mechanism of several distinct proteins: hirudin (a thrombin specific inhibitor), tick anticoagulant peptide (a factor Xa specific inhibitor), epidermal growth factor, insulin-like growth factor and a number of chemokines.
Experimentally, this requires the application of sophisticated technology, such as mass spectrometer and automated protein sequencer for the isolation and structural characterization of heterogeneous folding intermediates. The goal is to determine the pathway of the formation of the native structures and the non-covalent forces that guide this process.
Another major project of this Center is to develop new technologies to facilitate structural characterization of proteins that lost their native structures (denatured proteins). This laboratory has developed a novel methodology that permits denatured proteins to be trapped as disulfide isomers, which can be subsequently isolated for structural characterization.
This new method is currently being applied to analyze the unfolding pathway of the proteins mentioned above. Knowledge obtained from these studies will help us to understand diseases that are associated with defective protein folding and protein conformational change, such as prion related diseases.
University of Texas
Institute of Molecular Medicine
Research Center for Protein Chemistry