University of Minnesota Duluth
University of Minnesota Department of Chemistry and Biochemistry
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Friday, March 5, 2015; 3:00 p.m.; Chem 200 (Kobilka Lecture Hall)


Department of Chemistry & Biochemistry Welcomes:

Dr. Kathryn Splan

Associate Professor, Department of Chemistry, Macalester College



“Copper(I)-Binding Properties of the X-linked Inhibitor of Apoptosis Protein (XIAP) and other Zinc(II)-binding Domains”

Recent studies1 have indicated that the X-linked Inhibitor of Apoptosis Protein (XIAP), which is a key regulator of programmed cell death, may also function as a cellular copper sensor. Specifically, XIAP regulates intracellular concentrations of the copper exporter COMMD1 and binds copper ions directly. We have characterized the binding of copper to a construct of XIAP containing the BIR2 and BIR3 domains, both of which contain a thiol-rich zinc-binding structural site. Absorption and emission spectroscopic measurements show that Cu(I) binds at both the zinc structural sites within the protein and also at a higher affinity, surface-accessible binding site on the BIR2 domain. Moreover, binding at the BIR2 domain induces protein oligomerization, which is likely to impact the function of XIAP. These results constitute the first spectroscopic evidence for copper-XIAP interactions.2 We have also demonstrated that, although the zinc-binding sites within XIAP are not the primary binding site for copper, other structural zinc-binding sites, including those found within zinc finger (ZF) proteins, are susceptible to copper displacement. 3 These results suggested a possible role for Cu(I)-substituted zinc-binding domains in the context of both copper toxicity and copper-responsive transcription factors.