ACBD3

ACBD3 (acyl‑CoA binding domain containing 3) is a eukaryotic protein encoded by the ACBD3 gene in humans. The protein is a modular scaffold that localizes predominantly to the trans‑Golgi network and the smooth endoplasmic reticulum. It contains an N‑terminal acyl‑CoA binding domain followed by a GOLD domain, which is implicated in protein–protein interactions.

ACBD3 interacts with phosphatidylinositol 4‑kinase IIIβ (PI4KIIIβ) and the scaffold protein PI4KA, facilitating the assembly of a complex that generates phosphatidylinositol 4‑phosphate at Golgi membranes. This activity is essential for membrane trafficking, lipid homeostasis, and the regulation of innate immunity. The protein also binds to and recruits the host protein SKP1 in a process that modulates cullin‑3‑based ubiquitin ligase activity.

In the context of viral replication, ACBD3 has been identified as a crucial host factor for positive‑strand RNA viruses, particularly coronaviruses. The viral non‑structural protein 6 (nsp6) binds ACBD3, co‑opt­ing the PI4KIIIβ complex to create replication organelles enriched in phosphatidyl‑inositol 4‑phosphate. This interaction is essential for efficient viral RNA synthesis and is considered a potential antiviral target.

ACBD3 functions also involve the formation of membrane contact sites between the endoplasmic reticulum and the Golgi apparatus, thus influencing lipid transfer and organelle dynamics. Mutations or altered expression of ACBD3 are associated with developmental deficits and are being investigated for their role in metabolic disorders. The protein is highly conserved across vertebrates, underscoring its fundamental role in cell biology.