A hydrodynamic analysis of APOBEC3G reveals a monomer-dimer-tetramer self-association that has implications for anti-HIV function.
The innate antiviral factor APOBEC3G (A3G) possesses RNA binding activity and deaminates HIV-1 DNA. High-molecular mass forms of A3G can be isolated from a variety of cell types but exhibit limited deaminase activity relative to low-molecular mass species prepared under RNA-depleted conditions. To investigate the fundamental oligomeric state and shape of A3G, we conducted sedimentation velocity analyses of the pure enzyme under RNA-deficient conditions. The results reveal a predominant dimer in equilibrium with minor monomeric and tetrameric species. Hydrodynamic modeling of the dimer supports an extended cylindrical shape that assembles into an elongated tetramer. Overall, the results provide physical restraints for the A3G quaternary structure that have implications for modulating antiviral function.
Salter
Jason D
JD
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester, 601 Elmwood Avenue, Box 712, Rochester, New York 14642, USA.
Krucinska
Jolanta
J
Raina
Jay
J
Smith
Harold C
HC
Wedekind
Joseph E
JE
D000071480:APOBEC-3G Deaminase; D019380:Anti-HIV Agents / Q000494:pharmacology*; D001704:Biopolymers / Q000737:chemistry*; D003564:Cytidine Deaminase / Q000737:chemistry*; D008958:Models, Molecular; D008970:Molecular Weight
D019380:Anti-HIV Agents; D001704:Biopolymers; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase