Valjean R. Bascot-Davis, PhD

Research Title: Structure and Dynamics of the Encephalomyocarditis Virus Leader Protein in Deregulation of Host Nucleocytoplasmic Transport

Research Description: Valjean Bacot-Davis’ research project involved the main anti-host protein of Encephalomyocarditis virus (EMCV), known as the Leader (L) protein, and its activity in interferon inhibition during virus infection. While supported by this Virology Training Grant, Valjean completed the resolution of six protein structures using nuclear magnetic resonance. He solved the structure of: unphosphorylated L (L0P), singly-phosphorylated L (L1P), and double-phosphorylated L (L2P). L protein phosphorylation is known to enhance L activity during virus infection as well as enhance inhibition of the host immune response. He also solved the structure of the eukaryotic protein, Ran GTPase (Ran), known to interact with L during virus infection. Valjean solved the structure of Ran alone, Ran bound to L, and L bound to Ran to determine the structure of the L-Ran complex. The elucidation of these protein structures reveal that L uses a novel mechanism to interact with Ran in order to recruit host kinases, hyperphosphorylate nucleoporins of the nuclear pore complex, and swiftly suppress interferon activation of an anti-viral immune response. Furthermore, Valjean and colleagues solved the solution structure of Ran by NMR. This new structure offers compelling evidence of nucleosome involvement during RCC1-facilitated nucleotide exchange of Ran during eukaryotic nucleocytoplasmic trafficking. Elucidation of the L-Ran complex details a mechanism that could also help L be used for the development of anticancer therapies via targeted, nanoparticle, peptide delivery.

Dr. Bacot-Davis is continuing his training as a postdoctoral trainee at the University of Albany in the Department of Biological Sciences.