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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.
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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). | |
PubMed ID | 28716805 | |
DOI | 10.15252/embj.201796476 |
2 | Authors | Lee A.-R. Hwang J. Hur J.H. Ryu K.-S. Kim K.K. Choi B.-S. Kim N.-K. |
Title | Lee J.-H. 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). | |
PubMed ID | 30592616 | |
DOI | 10.1021/acschembio.8b00914 |
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). | |
PubMed ID | 11524677 | |
DOI | 10.1038/nsb0901-761 |
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). | |
PubMed ID | 27265117 | |
DOI | 10.1002/1873-3468.12238 |