The Zα domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA

The Zα domain of the editing enzyme dsRNA adenosine deaminase binds left-handed Z-RNA as well as Z-DNA

^*Department of Biology and ^†George R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139

Communicated by Alexander Rich

Abstract

The Zα domain of human double-stranded RNA adenosine deaminase 1 binds specifically to left-handed Z-DNA and stabilizes the Z-conformation. Here we report spectroscopic and analytical results that demonstrate that Zα can also stabilize the left-handed Z-conformation in double-stranded RNA. Zα induces a slow transition from the right-handed A-conformation to the Z-form in duplex r(CG)₆, with an activation energy of 38 kcal mol⁻¹. We conclude that Z-RNA as well as Z-DNA can be accommodated in the tailored binding site of Zα. The specific binding of Z-RNA by Zα may be involved in targeting double-stranded RNA adenosine deaminase 1 for a role in hypermutation of RNA viruses.

Footnotes

↵ ‡ To whom reprint requests should be addressed at: Department of Biology, Massachusetts Institute of Technology, Building 68, Room 233, Cambridge, MA 02139. E-mail: cbeckman{at}mit.edu.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.240464097.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.240464097
Abbreviations:

ADAR1,

double-stranded RNA adenosine deaminase 1;

ds,

double-stranded