A CYS3His zinc-binding domain from Nup475/Tristetraprolin:: A novel fold with a disklike structure

Nup475 (also known as tristetraprolin and TIS11) includes two zinc-binding domains of the form CYS-X-8-CYS-X-5-CYS-X-3-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 similar to25 Angstrom and a width of similar to12 Angstrom. This structure provides a basis for evaluating the role of individual residues for structural stability and for nucleic acid binding.