GMaP PILOT: 2020 GMaP Stimulus Award for Caroline Smith: Identification of Novel PRL-3 Inhibitors

PRL-3 is an oncogenic phosphatase that promotes metastasis in multiple tumor types including colorectal, breast, ovarian, and leukemias. However, the function of PRL-3 in normal and cancer cells is widely unknown, largely due to a lack of tools available to study the protein. Our lab has generated seven novel alpaca-derived anti-PRL-3 nanobodies to help aid in the determination of PRL-3 function. We must map the epitopes of these nanobodies on PRL-3 to determine how they may alter protein function and conformation. To map these sites, we will utilize both hydrogen deuterium exchange mass spectrometry and x-ray crystallography to confidently assess both structural and conformational aspects of PRL-3. These findings will determine if nanobodies can act as PRL-3 inhibitors themselves and provide structural information that will be useful for future PRL-3 drug design.