title: Kobuviral Non-structural 3A Proteins Act as Molecular Harnesses to Hijack the Host ACBD3 Protein.
abstract: Picornaviruses are small positive-sense single-stranded RNA viruses that include many important human pathogens. Within the host cell, they replicate at specific replication sites called replication organelles. To create this membrane platform, they hijack several host factors including the acyl-CoA-binding domain-containing protein-3 (ACBD3). Here, we present a structural characterization of the molecular complexes formed by the non-structural 3A proteins from two species of the Kobuvirus genus of the Picornaviridae family and the 3A-binding domain of the host ACBD3 protein. Specifically, we present a series of crystal structures as well as a molecular dynamics simulation of the 3A:ACBD3 complex at the membrane, which reveals that the viral 3A proteins act as molecular harnesses to enslave the ACBD3 protein leading to its stabilization at target membranes. Our data provide a structural rationale for understanding how these viral-host protein complexes assemble at the atomic level and identify new potential targets for antiviral therapies.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic. Electronic address: klima@uochb.cas.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Klima
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
authors.forename: Dominika
authors.initials: D
authors.lastname: Chalupska
authors.affiliation: Institute of Physics, Polish Academy of Sciences, 02-668 Warsaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Różycki
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Humpolickova
authors.affiliation: Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institute, 5232 Villigen PSI, Switzerland.
authors.forename: Lenka
authors.initials: L
authors.lastname: Rezabkova
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Silhan
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
authors.forename: Adriana
authors.initials: A
authors.lastname: Baumlova
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Dubankova
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, 16610 Prague, Czech Republic. Electronic address: boura@uochb.cas.cz.
authors.forename: Evzen
authors.initials: E
authors.lastname: Boura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D052699:Kobuvirus / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053835:Unilamellar Liposomes / Q000737:chemistry*; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: C449459:ACBD3 protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011994:Recombinant Proteins; D053835:Unilamellar Liposomes; D017361:Viral Nonstructural Proteins
keywords: 3A; ACBD3; Aichivirus; GOLD; Kobuvirus; molecular dynamics simulations; structure