Publication
Article Metrics
Citations
Online attention
Structural and hydrodynamic characterization of dimeric human oligoadenylate synthetase 2
DOI:
10.1016/j.bpj.2020.04.025
Authors:
Amit
Koul
(University of Manitoba)
,
Darren
Gemmill
(University of Lethbridge)
,
Nikhat
Lubna
(University of Manitoba)
,
Markus
Meier
(University of Manitoba)
,
Natalie
Krahn
(Yale University)
,
Evan P.
Booy
(University of Manitoba)
,
Jörg
Stetefeld
(University of Manitoba)
,
Trushar R.
Patel
(University of Lethbridge; University of Calgary; University of Alberta)
,
Sean A.
Mckenna
(University of Manitoba)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Biophysical Journal
State:
Published (Approved)
Published:
May 2020
Diamond Proposal Number(s):
16028
,
22113
Abstract: Oligoadenylate 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.
Diamond Keywords: Enzymes
Subject Areas:
Biology and Bio-materials,
Chemistry
Instruments:
B21-High Throughput SAXS
Added On:
21/05/2020 13:30
Documents:
1-s2.0-S0006349520303696-main.pdf
Discipline Tags:
Biochemistry
Catalysis
Chemistry
Structural biology
Biophysics
Life Sciences & Biotech
Technical Tags:
Scattering
Small Angle X-ray Scattering (SAXS)