|PROSITE documentation PDOC50139|
Nucleic acids form double-stranded helices. Double-stranded (ds) DNA typically adopts the so-called B-conformation, while dsRNA is usually in the A-conformation. Both DNA and RNA can also adopt a Z-form double helix that is characterized by a left-handed helical arrangement, a zigzag pattern of the phosphodiester backbone and the absence of major grooves. Z-DNA is believed to play a role in transcription by relieving torsional strain induced within the DNA template by the movement of RNA polymerases, and Z-DNA may also promote genetic instability. Physiological functions of Z-RNA remain unknown. The Z-binding domain (ZBD), also referred to as Zα or Zβ is a 78-amino-acid protein fold that specifically binds to Z-DNA as well as to Z-RNA but not to B-DNA. ZBDs have been identified in four proteins: ADAR1, ZBP1, E3L and PKZ. ADAR1 and ZBP1 are mammalian proteins implicated in antiviral innate immune responses. E3L is a poxvirus protein known to antagonise this host response. Lastly, PKZ is a fish protein related to mammalian PKR, also involved in antiviral immunity. This suggests an important role of ZBDs in innate antiviral immune responses and may imply that Z-DNA and/or Z-RNA trigger such a host defense response [1,2,3,4].
The Z-binding domain displays an α/β architecture with three α-helices packed against three antiparallel β-strands (see <PDB:1J75>). It belongs to the winged helix–turn–helix (wHTH) domain superfamily. The three helices form the core of the domain, with helices 2 and 3 forming the helix-turn-helix unit. Helix 1 is joined to helix 2 by a β-strand, β1. C-terminal to helix 3 is the ‘wing’, formed by two antiparallel β-strands (β2 and β3), which hydrogen bond to each another and to β1, forming a three-stranded β-sheet [3,4].
Protein currently known to include a Z-binding domain are listed below:
The profile we developed covers the entire Z-binding domain.Last update:
April 2020 / Profile and text revised.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Maelfait J. Liverpool L. Bridgeman A. Ragan K.B. Upton J.W. Rehwinkel J.|
|Title||Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis.|
|Source||EMBO. J. 36:2529-2543(2017).|
|2||Authors||Lee A.-R. Hwang J. Hur J.H. Ryu K.-S. Kim K.K. Choi B.-S. Kim N.-K. Lee J.-H.|
|Title||NMR Dynamics Study Reveals the Zalpha Domain of Human ADAR1 Associates with and Dissociates from Z-RNA More Slowly than Z-DNA.|
|Source||ACS. Chem. Biol. 14:245-255(2019).|
|3||Authors||Schwartz T. Behlke J. Lowenhaupt K. Heinemann U. Rich A.|
|Title||Structure of the DLM-1-Z-DNA complex reveals a conserved family of Z-DNA-binding proteins.|
|Source||Nat. Struct. Biol. 8:761-765(2001).|
|4||Authors||Subramani V.K. Kim D. Yun K. Kim K.K.|
|Title||Structural and functional studies of a large winged Z-DNA-binding domain of Danio rerio protein kinase PKZ.|
|Source||FEBS. Lett. 590:2275-2285(2016).|