3IRR

Crystal Structure of a Z-Z junction (with HEPES intercalating)

Summary for 3IRR

• Entry DOI: 10.2210/pdb3irr/pdb
• Related: 1QBJ 3IRQ
• Descriptor: Double-stranded RNA-specific adenosine deaminase, DNA (5'-D(*G*TP*CP*GP*CP*GP*CP*GP*TP*CP*GP*CP*GP*CP*G)-3'), DNA (5'-D(*A*CP*CP*GP*CP*GP*CP*GP*AP*CP*GP*CP*GP*CP*G)-3'), ... (5 entities in total)
• Functional Keywords: z-dna, adar1, rna editing, innate immunity, dna junction, z domain, intercalation, alternative promoter usage, alternative splicing, cytoplasm, disease mutation, dna-binding, hydrolase, isopeptide bond, metal-binding, mrna processing, nucleus, phosphoprotein, polymorphism, rna-binding, rna-mediated gene silencing, ubl conjugation, zinc, hydrolase-dna complex, hydrolase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P55265
• Total number of polymer chains: 6
• Total formula weight: 38912.56

Authors

Athanasiadis, A.,de Rosa, M. (deposition date: 2009-08-24, release date: 2010-05-19, Last modification date: 2023-09-06)

Primary citation

de Rosa, M.,de Sanctis, D.,Rosario, A.L.,Archer, M.,Rich, A.,Athanasiadis, A.,Carrondo, M.A.
Crystal structure of a junction between two Z-DNA helices.
Proc.Natl.Acad.Sci.USA, 107:9088-9092, 2010

PubMed Abstract: The double helix of DNA, when composed of dinucleotide purine-pyrimidine repeats, can adopt a left-handed helical structure called Z-DNA. For reasons not entirely understood, such dinucleotide repeats in genomic sequences have been associated with genomic instability leading to cancer. Adoption of the left-handed conformation results in the formation of conformational junctions: A B-to-Z junction is formed at the boundaries of the helix, whereas a Z-to-Z junction is commonly formed in sequences where the dinucleotide repeat is interrupted by single base insertions or deletions that bring neighboring helices out of phase. B-Z junctions are shown to result in exposed nucleotides vulnerable to chemical or enzymatic modification. Here we describe the three-dimensional structure of a Z-Z junction stabilized by Zalpha, the Z-DNA binding domain of the RNA editing enzyme ADAR1. We show that the junction structure consists of a single base pair and leads to partial or full disruption of the helical stacking. The junction region allows intercalating agents to insert themselves into the left-handed helix, which is otherwise resistant to intercalation. However, unlike a B-Z junction, in this structure the bases are not fully extruded, and the stacking between the two left-handed helices is not continuous.

PubMed: 20439751
DOI: 10.1073/pnas.1003182107

Experimental method

X-RAY DIFFRACTION (2.65 Å)