Biochemistry and Biophysics
Office: 552 Science and Technology Building
Telephone: (252) 328-9790
Fax: (252) 328-6210
Department of Chemistry
|Postdoctoral Researcher, University of
California at Santa Cruz, 2000-2003
NIH Postdoctoral Researcher, University of California at Santa Cruz, 1998-2000
Ph.D. Chemistry, University of North Carolina at Chapel Hill, 1998
B.A., Kenyon College, 1993
|Research Interests: Characterizing metal binding sites in proteins|
Research in the Burns lab focuses on elucidating the metal binding motifs “natively unfolded” proteins use and on characterizing the effect metal binding has on the overall structure of the protein. Ultimately, the goal is to understand protein function, and possibly misfunction, on a molecular level. The structure and function of proteins is investigated using peptide synthesis, recombinant DNA methodology, and spectroscopy. Magnetic resonance serves as a prime spectroscopic method in these studies, specifically one and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and electron paramagnetic resonance (EPR) spectroscopy. Many of proteins we plan to examine are involved in devastating neurological diseases.
The proteins I am most interested in are either unfolded or adopt non-globular structures under physiological conditions. Proteins such as these are referred to as “natively unfolded.” Many proteins belonging to this class coordinate metal ions. This raises two important questions: What types of metal binding motifs do natively unfolded proteins have? And do they differ significantly from those of folded proteins? Interestingly, a number of these proteins are implicated in disease, including Alzheimer’s disease, Parkinson’s disease, and Mad Cow’s disease. Recent research suggests there may be a link between metal homeostasis and disease.
For the last several years I have been
examining Cu2+ binding in the prion protein (PrP). PrP
is responsible for a class of fatal neurological diseases called transmissible
spongiform encephalopathies (TSE’s). Recent studies suggest that
PrP is involved with copper homeostasis within the central nervous system.
The majority of copper binding takes place in a domain composed of repeating
PHGGGWGQ sequences, where the underlined residues directly coordinate
Cu2+. In collaboration with other researchers, we have
identified the structure of the major Cu2+ binding site in PrP
|With this structural information, we can
begin to critically evaluate hypotheses regarding the normal physiological
function of PrP and the interplay between improper metal ion regulation
and neurological disease.
a-Synuclein belongs to the family of natively unfolded proteins and is abundant in various regions of the brain. The normal function of a-syn is unknown, but deposition of a-syn aggregates is a pathological hallmark of Parkinson’s disease. It has been demonstrated that a-syn interacts with Cu2+ and that this metal ion greatly increases the rate of aggregation. The nature and structure of the a-syn-Cu2+ interaction will be elucidated using peptide design, recombinant DNA methodology, and EPR spectroscopy.
East Carolina University
Greenville, NC 27858