Inactivation of SCF Ligase Inhibits RVFV


dekokmercado_f_16A-1

Category: A-1 Didactic/Instructional – Non-commercial

Title of entry: Inactivation of SCF Ligase Inhibits RVFV

Entrant’s name: Fabian de Kok-Mercado

Membership Type: Professional

Address: Ellicott City, MD

Client: Virology Lab

Medium / software used: Adobe Photoshop, Maxon Cinema 4D, ePMV

Final presentation format: Scientific Journal Graphical Abstract

Primary audience: Virologists and Molecular Biologists

Intended purpose: The purpose of this illustration is to visually summarize the results of a  study on the replication of the Rift Valley Fever virus (RVFV), which is shown entering the scene  from the top. The left side depicts how the NSswt protein encoded by RVFV promotes early PKR  proteasomal degradation by assembling the SCF ligase. PKR is ubiquitinated (Ub) by the SCF’s E2  enzyme and is then targeted for degradation. The study also investigated disruptions of this  process, shown on the right. NSsGE, an NSs degron viral mutant that prevents NSs-FBXW11  interactions, and MLN4924, a small molecule inhibitor that binds to NEDD8, are both shown  inhibiting SCF assembly. The bottom right inset shows that when PKR degradation is blocked,  NSsGE activates PKR, which then auto-phosphorylates and subsequently phosphorylates EIF2A.  Accumulation of phosphorylated EIF2A shuts down ongoing protein synthesis including viral gene  translation leading to inhibition of RVFV infection.