Raquel L. Liberman, PhDBACK

Assistant Professor, Georgia Tech

Crystal Structure of an Intramembrane Asparyl Protease

Presenilin is a critical component of a large enzyme complex that plays a key role in producing, from a precursor protein, the range of peptides (strings of amino acids) that form the amyloid substances found in plaques, blood vessels and neurons of the brains of patients with Alzheimer's disease (AD). This complex is very challenging to study by methods that would allow its atomic structure to be revealed. Dr. Lieberman's research will focus on the discovery of the atomic structure of an enzyme in the same family as presenilin. To accomplish this, she will produce the model enzyme using recombinant DNA technology, purify it by column chromatography, grow crystals of the enzyme and then use the crystals to collect X-ray diffraction data, creating a three dimensional molecular structure. By studying the structure of the related model protein, which can work independently to produce similar peptide fragments, she will better understand the chemistry behind how the presenilin complex cleaves the amyloid precursor protein to form amyloid peptides. With an experimentally-determined three-dimensional atomic structure of an enzyme capable of producing amyloidogenic peptides, she will gain tremendous insight into its biochemistry and function. The results can lead to new experiments in vitro, in cells, and in animals to better understand the role of peptide cleavage in AD, thus offering new ways to approach treatments to control amyloid peptide formation in AD patients.