Did you know that metals play important roles in our health? You may have heard of some essential metals, like Ca, K, Fe, and Zn. And you probably know of some metals that are toxic, like Pb and Hg. Other metals can be used as medicines, like Pt drugs that treat cancer. Did you know that copper (Cu) is essential to your health? Cu is used in just about every cellular and systematic process including formation of connective tissues, cellular energy production (ATP), and neurotransmission.
One of the reasons copper is essential is because it has the ability to change oxidation states in biological environments. Cu can absorb and give off electrons by changing its oxidation state (its charge). The two most common oxidation states in biology are the +1 and +2 states. This changing in oxidation state is called redox chemistry and it allows copper to mediate some of the electron transfer reactions that are essential for things like cellular energy production (in the electron transport chain) and antioxidant activity in cytoplasm and in body fluids (SOD 1 and SOD 3).
This redox chemistry is essential, however it can also be toxic if it is not controlled. If Cu is allowed to cycle like this unchecked, it can cause significant damage through oxidative stress. There is speculation and scientific data that suggest that malfunction of our bodies’ copper-handling proteins may result in neurodegenerative diseases like Alzheimer’s, Parkinson’s and prion diseases. The Haas Lab focuses on understanding how our proteins use copper for good while protecting against the bad, and we are working toward understanding what role copper may have in Alzheimer’s disease.
Because Cu is absolutely essential, yet potentially toxic if it is not regulated, human proteins have evolved with very specific sites to cary copper in a controlled way. This means that they have a certain number of ligands (binding groups) that hold the copper in a certain geometry and in a specific oxidation state so that it can’t cycle the Cu is transported in the body. Our lab focuses on proteins that handle Cu in your body. Our main focus is on the human copper transport protein (called Ctr1).
The Ctr1 protein allows Cu to pass safely through the membrane of your cells, but to do so, it must change its oxidation state. Ctr1 must be very good at allowing this Cu oxidation state change while protecting against bad redox chemistry. There is almost nothing known about how this happens: which other proteins are involved, what are the binding site geometries and ligands, where does the electron come from, how fast does it happen? We aim to find the answers to these questions through research in the Haas lab at Saint Mary’s College.
Click on the video below to learn a bit about the Ctr1 protein!