The solution structure of the N-terminal domain of E3L shows a tyrosine conformation that may explain its reduced affinity to Z-DNA in vitro

J.D. Kahmann, D.A. Wecking, V. Putter, K. Lowenhaupt, Y.G. Kim, P. Schmieder, H. Oschkinat, A. Rich, M. Schade

Proc. Natl. Acad. Sci. USA (2004) 101, 2712-2717

The N-terminal domain of the vaccinia virus protein E3L (ZalphaE3L) is essential for full viral pathogenicity in mice. It has sequence similarity to the high-affinity human Z-DNA-binding domains ZalphaADAR1 and ZalphaDLM1. Here, we report the solution structure of ZalphaE3L and the chemical shift map of its interaction surface with Z-DNA. The global structure and the Z-DNA interaction surface of ZalphaE3L are very similar to the high-affinity Z-DNA-binding domains ZalphaADAR1 and ZalphaDLM1. However, the key Z-DNA contacting residue Y48 of ZalphaE3L adopts a different side chain conformation in unbound ZalphaE3L, which requires rearrangement for binding to Z-DNA. This difference suggests a molecular basis for the significantly lower in vitro affinity of ZalphaE3L to Z-DNA compared with its homologues.