Cottrell Scholar Awards - 2016
Transporting Cu(I) as Cargo and Using Cu(III) as a Killer Cofactor: Histidine-rich Motifs in Ctr1 and Histatin 5 Control Cu Oxidation State and Reactivity
Our bodies are continually undergoing vital chemical and electrical activities, none of which could occur without the trace minerals in our food. One of those is the metal copper, which plays a versatile role in maintaining human health.
Kathryn L. Haas, assistant professor of chemistry, Saint Mary’s College, is investigating the subtle ways the body maintains the proper balance of copper.
Our cells acquire copper primarily through the cell membrane with the help of a protein-based transporter molecule, Ctr1. A short piece of this protein molecule, or peptide, also appears to guard against copper atoms losing or adding stray electrons in what is known generally as an oxidation-reduction reaction (redox, for short). Meanwhile, another peptide, Histatin 5 (Hist5), found in saliva, makes use of a copper-catalyzed reaction to fight disease-causing fungi.
“Ctr1 and Hist5 serve different biological roles, but have interesting parallels in their use of similar histidine-rich coordination motifs in controlling copper reactivity,” Haas notes. Histidine is an amino acid, a basic chemical building block the body uses to create proteins, which do much of the work in living cells.
Haas and her undergraduate students will investigate histidine-rich regions of the Ctr1 and Hist5 peptides. They aim to uncover new knowledge about the chemical mechanisms by which Ctr1 manipulates its vital cargo of copper, and the methods by which Hist5 modifies and employs copper to kill pathogenic fungi.
“Fundamental understanding of the chemical principles by which Ctr1 and Hist5 control copper reactivity has broader application in the design of new peptide antibiotics and therapeutics for treatment of copper-related disorders,” Haas said. Those include Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis and prion diseases.
For the education component of the Cottrell Scholar Award, Haas is developing a “Video Web” to enable students to understand scientific concepts and to prepare for upcoming classes. Videos will be placed on YouTube and will be linked to each other using the YouTube Annotations feature. “The Video Web will empower students to take control of their education and integrate discipline-specific concepts into their open-ended, interdisciplinary laboratory projects,” Haas said.