Structural and hydrodynamic characterization of dimeric human oligoadenylate synthetase 2

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dc.contributor.authorKoul, Amit
dc.contributor.authorGemmill, Darren L.
dc.contributor.authorLubna, Nikhat
dc.contributor.authorMeier, Markus
dc.contributor.authorKrahn, Natalie
dc.contributor.authorBooy, Evan P.
dc.contributor.authorStetefeld, Jörg
dc.contributor.authorPatel, Trushar R.
dc.contributor.authorMcKenna, Sean A.
dc.date.accessioned2023-05-02T18:07:12Z
dc.date.available2023-05-02T18:07:12Z
dc.date.issued2020
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
dc.description.abstractOligoadenylate synthetases (OASs) are a family of interferon-inducible enzymes that require double-stranded RNA (dsRNA) as a cofactor. Upon binding dsRNA, OAS undergoes a conformational change and is activated to polymerize ATP into 2′-5′-oligoadenylate chains. The OAS family consists of several isozymes, with unique domain organizations to potentially interact with dsRNA of variable length, providing diversity in viral RNA recognition. In addition, oligomerization of OAS isozymes, potentially OAS1 and OAS2, is hypothesized to be important for 2′-5′-oligoadenylate chain building. In this study, we present the solution conformation of dimeric human OAS2 using an integrated approach involving small-angle x-ray scattering, analytical ultracentrifugation, and dynamic light scattering techniques. We also demonstrate OAS2 dimerization using immunoprecipitation approaches in human cells. Whereas mutation of a key active-site aspartic acid residue prevents OAS2 activity, a C-terminal mutation previously hypothesized to disrupt OAS self-association had only a minor effect on OAS2 activity. Finally, we also present the solution structure of OAS1 monomer and dimer, comparing their hydrodynamic properties with OAS2. In summary, our work presents the first, to our knowledge, dimeric structural models of OAS2 that enhance our understanding of the oligomerization and catalytic function of OAS enzymes.
dc.identifier.citationKoul, A., Gemmill, D., Lubna, N., Meier, M., Krahn, N., Booy, E. P., Stetefeld, J., Patel, T. R., & McKenna, S. A. (2020). Structural and hydrodynamic characterization of dimeric human oligoadenylate synthetase 2. Biophysical Journal, 118(11), 2726-2740. https://doi.org/10.1016/j.bpj.2020.04.025
dc.identifier.urihttps://hdl.handle.net/10133/6483
dc.language.isoen
dc.publisher.departmentDepartment of Chemistry and Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Manitoba
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionYale University
dc.publisher.institutionUniversity of Alberta
dc.publisher.institutionUniversity of Calgary
dc.subjectOligoadenylate synthetases
dc.subjectDimeric structure
dc.subjectHydrodynamic studies
dc.subjectOAS enzymes
dc.subject.lcshOligoadenylates
dc.titleStructural and hydrodynamic characterization of dimeric human oligoadenylate synthetase 2
dc.typeArticle
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