Structural insights into Acyl‐coenzyme A binding domain containing 3 (ACBD3) protein hijacking by picornaviruses

Abstract

Many picornaviruses hijack the Golgi resident Acyl-coenzyme A binding domain containing 3 (ACBD3) protein in order to recruit the phosphatidylinositol 4-kinase B (PI4KB) to viral replication organelles (ROs). PI4KB, once recruited and activated by ACBD3 protein, produces the lipid phosphatidylinositol 4-phosphate (PI4P), which is a key step in the biogenesis of viral ROs. To do so, picornaviruses use their small nonstructural protein 3A that binds the Golgi dynamics domain of the ACBD3 protein. Here, we present the analysis of the highly flexible ACBD3 proteins and the viral 3A protein in solution using small-angle X-ray scattering and computer simulations. Our analysis revealed that both the ACBD3 protein and the 3A:ACBD3 protein complex have an extended and flexible conformation in solution. K E Y W O R D SACBD3, coarse-grained simulations, host factor, intrinsically disordered regions, picornavirus, RNA virus, small-angle X-ray scattering (SAXS)

The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection

“…While PHB and APOLs seem to be part of an autophagy system linked to infection, PI4KB is likely to be associated with this system given involvement of this enzyme in both autophagy and viral replication [56,118–131]. Accordingly, PI4KB was found to be involved in autophagy linked to infection by group A Streptococcus [144].…”

Emerging Role for Acyl-CoA Binding Domain Containing 3 at Membrane Contact Sites During Viral Infection

“…Aichi virus (AiV), a member of the kobuvirus genus in the Picornaviridae family, is one of the pathogenic factors of gastroenteritis. Researchers demonstrated that the non-structural proteins 2B, 2BC, 2C, 3A, and 3AB from Aichi virus interacted with ACBD3 and PI4KB to form a protein complex at ROs to promote PI4P synthesis (Greninger et al, 2012;Sasaki et al, 2012;Klima et al, 2017;McPhail et al, 2017;Chalupska et al, 2019). Silencing of ACBD3 or PI4KB inhibited viral replication by about 70% (ACBD3) or 99% (PI4KB).…”

“…PI4KB localizes to the Golgi apparatus by interacting with ACBD3. In cells infected by AiV, the viral proteins 2B, 2BC, 2C, 3A, and 3AB compete with Golgi giantin to bind to ACBD3, causing viral protein/ACBD3/PI4KB formation, and the colocalization of giantin and ACBD3 disappears (Greninger et al, 2012;Sasaki et al, 2012;Klima et al, 2017;McPhail et al, 2017;Chalupska et al, 2019).…”

“…When it binds to the GOLD domain of ACBD3, the intrinsically disordered protein AiV 3A adopts a highly ordered structure and is targeted to the membrane (Klima et al, 2017;McPhail et al, 2017). Then, 3A recruits and activates PI4KB, resulting in the production of PI4P (Chalupska et al, 2019). Researchers have analyzed the conformation of the ACBD3 protein and viral 3A protein in solution by using small angle X-ray scattering (SAXS) and computer simulation (Rozycki and Boura, 2014;Peti et al, 2018).…”

“…Researchers have analyzed the conformation of the ACBD3 protein and viral 3A protein in solution by using small angle X-ray scattering (SAXS) and computer simulation (Rozycki and Boura, 2014;Peti et al, 2018). Both the ACBD3 protein and the 3A:ACBD3 protein complex exhibit extended and flexible conformations in solution (Chalupska et al, 2019).…”