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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 9; pp. 2712 - 2717
• Main Authors: Kahmann, Jan D., Wecking, Diana A., Putter, Vera, Lowenhaupt, Ky, Kim, Yang-Gyun, Schmieder, Peter, Oschkinat, Hartmut, Rich, Alexander, Schade, Markus
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.03.2004; National Acad Sciences
• Subjects: AE3L protein; Amino Acid Sequence; Atomic interactions; Atoms; Binding Sites; Biochemistry; Biological Sciences; Chemical equilibrium; Deoxyribonucleic acid; DNA; DNA, Z-Form - chemistry; E3L protein; Hydrogen bonds; Magnetic Resonance Spectroscopy - methods; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Pathogens; Protein Conformation; Proteins; Protons; RNA-Binding Proteins - chemistry; Rodents; Solution chemistry; Solutions; Tyrosine; Vaccinia virus; Viral Proteins - chemistry; Viruses; Z form DNA
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0308612100

The N-terminal domain of the vaccinia virus protein E3L ( ZαE3 L) is essential for full viral pathogenicity in mice. It has sequence similarity to the high-affinity human Z-DNA-binding domains ZαADAR1and ZαDLM1. Here, we report the solution structure of ZαE3 Land the chemical shift map of its interaction surface with Z-DNA. The global structure and the Z-DNA interaction surface of ZαE3 Lare very similar to the high-affinity Z-DNA-binding domains ZαADAR1and ZαDLM1. However, the key Z-DNA contacting residue Y48 of ZαE3 Ladopts a different side chain conformation in unbound ZαE3 L, which requires rearrangement for binding to Z-DNA. This difference suggests a molecular basis for the significantly lower in vitro affinity of ZαE3 Lto Z-DNA compared with its homologues.