5TDQ

Crystal Structure of the GOLD domain of ACBD3

Summary for 5TDQ

• Entry DOI: 10.2210/pdb5tdq/pdb
• Descriptor: Golgi resident protein GCP60 (1 entity in total)
• Functional Keywords: beta barrel, gold domain, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19214.14

Authors

McPhail, J.A.,Burke, J.E. (deposition date: 2016-09-19, release date: 2016-11-23, Last modification date: 2023-10-04)

Primary citation

McPhail, J.A.,Ottosen, E.H.,Jenkins, M.L.,Burke, J.E.
The Molecular Basis of Aichi Virus 3A Protein Activation of Phosphatidylinositol 4 Kinase III beta , PI4KB, through ACBD3.
Structure, 25:121-131, 2017

PubMed Abstract: Phosphatidylinositol 4-kinase III beta (PI4KIIIβ) is an essential enzyme in mediating membrane transport, and plays key roles in facilitating viral infection. Many pathogenic positive-sense single-stranded RNA viruses activate PI4KIIIβ to generate phosphatidylinositol 4-phosphate (PI4P)-enriched organelles for viral replication. The molecular basis for PI4KIIIβ activation during viral infection has remained largely unclear. We describe the biochemical reconstitution and characterization of the complex of PI4KIIIβ with the Golgi protein Acyl-coenzyme A binding domain containing protein 3 (ACBD3) and Aichi virus 3A protein on membranes. We find that 3A directly activates PI4KIIIβ, and this activation is sensitized by ACBD3. The interfaces between PI4KIIIβ-ACBD3 and ACBD3-3A were mapped with hydrogen-deuterium exchange mass spectrometry (HDX-MS). Determination of the crystal structure of the ACBD3 GOLD domain revealed a unique N terminus that mediates the interaction with 3A. Rationally designed complex-disrupting mutations in both ACBD3 and PI4KIIIβ completely abrogated the sensitization of 3A activation by ACBD3.

PubMed: 27989622
DOI: 10.1016/j.str.2016.11.016

Experimental method

X-RAY DIFFRACTION (2.493 Å)