INOR 758 |
| Zinc finger proteins mediate a wide variety of macromolecular interactions including gene regulation at both the transcriptional and translational levels. TTP (tristetraprolin, also named NUP475 and Tis11) belongs to a new class of zinc binding domains characterized by tandem CCCH repeats. TTP regulates the expression of a number of cytokines such as tumor necrosis factor alpha (proteins involved in inflammatory response) at the mRNA level. TTP accomplishes this regulation by binding to AU-rich sequence elements (AREs) located at the 3'untranslated region (3'UTR) of cytokine mRNA molecules forming a complex that is degraded by the exosome. As part of an effort to understand the macromolecular implications of sequence and the role of these novel zinc binding domains in RNA regulation, we have prepared peptides that correspond to the zinc binding domains of TTP (TTP-D1 and TTP-2D). Under in vitro expression conditions, TTP-2D acquires iron from the Luria Broth media, a phenomenon that we do not observe for other CCCH zinc binding protein family members. Using a combination of optical and fluorescence spectroscopies, we have determined that although TTP-2D requires that a metal ion be coordinated to the CCCH domains for function (RNA binding); the nature of the metal ion bound is flexible (1). We are currently delineating how the nature of the metal ion bound to TTP-2D affects its susceptibility to oxidation. (1) diTargiani RC, Lee SJ, Wassink S, Michel SLJ; “Functional characterization of iron-substituted tristetraprolin-2D (TTP-2D, NUP475-2D): RNA binding affinity and selectivity.” Biochemistry. 2006, Nov 14;45(45):13641-9. |
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Bioinorganic Chemistry: Enzymes and Coenzymes
7:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Inorganic Chemistry |