3eyi
The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA
Structural highlights
FunctionZBP1_HUMAN Participates in the detection by the host's innate immune system of DNA from viral, bacterial or even host origin. Plays a role in host defense against tumors and pathogens. Acts as a cytoplasmic DNA sensor which, when activated, induces the recruitment of TBK1 and IRF3 to its C-terminal region and activates the downstream interferon regulatory factor (IRF) and NF-kappa B transcription factors, leading to type-I interferon production. ZBP1-induced NF-kappaB activation probably involves the recruitment of the RHIM containing kinases RIPK1 and RIPK3 (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMammalian DAI (DNA-dependent activator of IFN-regulatory factors), an activator of the innate immune response, senses cytosolic DNA by using 2 N-terminal Z-DNA binding domains (ZBDs) and a third putative DNA binding domain located next to the second ZBD. Compared with other previously known ZBDs, the second ZBD of human DAI (hZbeta(DAI)) shows significant variation in the sequence of the residues that are essential for DNA binding. In this article, the crystal structure of the hZbeta(DAI)/Z-DNA complex reveals that hZbeta(DAI) has a similar fold to that of other ZBDs, but adopts an unusual binding mode for recognition of Z-DNA. A residue in the first beta-strand rather than residues in the beta-loop contributes to DNA binding, and part of the (alpha3) recognition helix adopts a 3(10) helix conformation. The role of each residue that makes contact with DNA was confirmed by mutational analysis. The 2 ZBDs of DAI can together bind to DNA and both are necessary for full B-to-Z conversion. It is possible that binding 2 DAIs to 1 dsDNA brings about dimerization of DAI that might facilitate DNA-mediated innate immune activation. The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA.,Ha SC, Kim D, Hwang HY, Rich A, Kim YG, Kim KK Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20671-6. Epub 2008 Dec 18. PMID:19095800[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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