Cu(I) Interactions with Zinc Finger Proteins: Disruption of Zinc Binding Sites in the RING Domain of XIAP and BRCA1

Authors

Isaiah Eckart-Frank, Macalester CollegeFollow

Document Type

Honors Project On-Campus Access Only

Abstract

Copper is an essential, but potentially toxic trace metal in biology. Therefore, organisms have evolved complex mechanisms to maintain safe cellular copper levels. One key player in copper homeostasis is X-linked inhibitor of apoptosis protein (XIAP), which uses its zinc containing RING domain to regulate cellular copper efflux. This thesis explores the interaction of Cu(I) with XIAP to investigate its molecular mechanism. In this project, XIAP-RING was successfully purified and characterized. UV-Vis and fluorescence spectroscopy methods were used to study the interactions between XIAP-RING and Cu(I), which showed that Cu(I) displaces Zn(II) bound to XIAP-RING with a ratio of two Cu(I) to one Zn(II). Further studies to investigate the effects of Cu(I) displacement on XIAP-RING indicate that Cu(I) disrupts the dimeric structure of XIAP-RING. These studies help to better understand how XIAP might regulate copper and provide insight into how copper interacts with native zinc proteins.

Recommended Citation

Eckart-Frank, Isaiah, "Cu(I) Interactions with Zinc Finger Proteins: Disruption of Zinc Binding Sites in the RING Domain of XIAP and BRCA1" (2020). Chemistry Honors Projects. 31.
https://digitalcommons.macalester.edu/chem_honors/31