Nup475 (also known as tristetraprolin and TIS11) includes two zinc-binding domains of the form Cys-X8-Cys-X5-Cys-C3-His. These domains are required for rapid degradation of tumor necrosis factor (TNF) and other mRNAs through the interaction with AU-rich elements in their 3′-untranslated regions. The three-dimensional solution structure of the first domain was determined by multidimensional nuclear magnetic resonance spectroscopy, revealing a novel fold around a central zinc ion. The core structure is disklike with a diameter of ∼25 Å and a width of ∼12 Å. This structure provides a basis for evaluating the role of individual residues for structural stability and for nucleic acid binding.
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