New Understanding of Flexible Structure of Interleukin-2 (IL-2) May Guide Drug Discovery

The signaling molecule interleukin-2 (IL-2) has long been known to have powerful effects on the immune system, but efforts to harness it for therapeutic purposes have been hampered by serious side effects. Now researchers have worked out the details of IL-2's complex interactions with receptor molecules on immune cells, providing a blueprint for the development of more targeted therapies for treating cancer or autoimmune diseases. IL-2 acts as a growth factor to stimulate the expansion of T cell populations during an immune response. Different types of T cells play different roles, and IL-2 can stimulate both effector T cells, which lead the immune system's attack on specific antigens, and regulatory T cells, which serve to rein in the immune system after the threat is gone. "IL-2 can act as either a throttle or a brake on the immune response in different contexts," said Nikolaos Sgourakis, PhD, Assistant Professor of Chemistry and Biochemistry at the University of California (UC), Santa Cruz. "Our investigation used detailed biophysical methods to show how it does this." Dr. Sgourakis is a corresponding author of the new study, published online on March 17, 2020 in PNAS. The article is titled “Interleukin-2 Druggability Is Modulated by Global Conformational Transitions Controlled by a Helical Capping Switch.” The first author, Viviane De Paula, PhD, a visiting scientist in his lab from the Federal University of Rio de Janeiro, used nuclear magnetic resonance spectroscopy (NMR) to observe IL-2's structural dynamics. The study was done in close collaboration with corresponding author Dr. Christopher Garcia's group at Stanford University. The researchers were able to show that IL-2 adopts two different structural forms (termed conformations) that affect how it interacts with the receptors on different types of T cells.
Login Or Register To Read Full Story