Proposed Article Title
Protein signaling is the key method by which cells recognize a stimulus from their environment and convert it into a response. Signaling occurs in many forms: hormones, growth factors, and even proteins may act as signals from the environment. The response to their detection must be carried from the cell surface, where the signal is detected, to the nucleus, where the cell alters its DNA expression. This study analyzes one component in the signaling pathway of Spleen Tyrosine Kinase (Syk). The Syk protein receives a signal from B-cell receptors and amplifies it, resulting in an adaptive immune response and the production of antibodies for targeting foreign molecules. Strikingly, constant amplification of the Syk signal can transform B-cells into a cancerous phenotype and has been associated with cancers of the lymphatic system. Syk has also been implicated in autoimmune diseases such as rheumatoid arthritis. This study uses nuclear magnetic resonance spectroscopy to determine the structure of a segment from the Syk protein bound to Vav1, a downstream signaling protein that has been implicated in various cancers. The preliminary result will be refined using a molecular dynamics simulation to obtain the most energetically stable conformation of the protein-ligand interaction. The terminal results of this experiment will reveal the structural details of the Syk-Vav1 interaction, which may describe a possible therapeutic target in the treatment of proliferative B-cell disorders, as well as some types of cancer. Using this information, one or more drugs may be synthesized to block the interaction in cancerous cells, providing a therapeutic avenue to treat the disease.
Piraner, Dan I.
"3D Picture of the SYK-VAV1 Protein Complex: Tracking the B-Cell Signal One Complex at a Time,"
The Journal of Purdue Undergraduate Research:
Vol. 1, Article 6.