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.
The N-terminal domain of the vaccinia virus protein E3L (Z alpha(E3L)) is essential for full viral pathogenicity in mice. It has sequence similarity to the high-affinity human Z-DNA-binding domains Z alpha(ADAR1) and Z alpha(DLM1). Here, we report the solution structure of Z alpha(E3L) and the chemical shift map of its interaction surface with Z-DNA. The global structure and the Z-DNA interaction surface of Z alpha(E3L) are very similar to the high-affinity Z-DNA-binding domains Z alpha(ADAR1) and Z alpha(DLM1). However, the key Z-DNA contacting residue Y48 of Z alpha(E3L) adopts a different side chain conformation in unbound Z alpha(E3L), which requires rearrangement for binding to Z-DNA. This difference suggests a molecular basis for the significantly lower in vitro affinity of Z alpha(E3L) to Z-DNA compared with its homologues.
Combinature Biopharm AG, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.
Jan D
JD
Kahmann
Diana A
DA
Wecking
Vera
V
Putter
Ky
K
Lowenhaupt
Yang-Gyun
YG
Kim
Peter
P
Schmieder
Hartmut
H
Oschkinat
Alexander
A
Rich
Markus
M
Schade
D000595:Amino Acid Sequence; D001665:Binding Sites; D043542:DNA, Z-Form / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry*; D012996:Solutions; D014443:Tyrosine; D014764:Viral Proteins / Q000737:chemistry*
D043542:DNA, Z-Form; C081374:E3L protein, Vaccinia virus; D016601:RNA-Binding Proteins; D012996:Solutions; D014764:Viral Proteins; D014443:Tyrosine