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Insight Into Copper Uptake from the Three-Dimensional Structure of the Human Copper Transporter

Insight Into Copper Uptake from the Three-Dimensional Structure of the Human Copper Transporter


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About the Book

The copper uptake transporter (CTR) family of membrane proteins, found ubiquitously in eukaryotes, is required for the cellular uptake of the essential metal ion copper. Biochemical and structural studies have shown that these proteins contain three transmembrane domains, oligomerize into trimers, and contain a central pore believed to be the pathway for copper uptake. However, it is not known how this putative pore is constructed by the TMs, because there have been very few studies that have investigated the functional and structural role of the membrane domain. Furthermore, it is not well understood how the pore can mechanistically transport copper and, at the same time, regulate its unwanted accumulation in the cytosol. I have designed my thesis project goals to uncover the structural and functional roles of TM packing in CTRs in order to better understand how copper uptake occurs through CTR proteins. While a high-resolution structure would be ideal, this still remains a difficult accomplishment for membrane proteins, especially those proteins, like the CTR family, which have no prokaryotic homologues. In order to accomplish the goals of my thesis, I chose two complementary approaches in order to maximize the amount of insight gained, since membrane protein structural biology projects tend to be difficult. The first approach was to solve the full 3D structure of hCTR1 by cryo-electron microscopy from 2D crystals that our lab has been able to obtain. The second approach was to use tryptophan-scanning mutagenesis to identify packing interfaces within the membrane domain of different CTRs. The results of my two approaches has led to a TM packing model for how the membrane domain is arranged in CTRs and has provided insight into the role and spatial juxtaposition of extramembraneous domains relative to the pore. In all, my thesis work, together with contributions from our collaborators, provides a new framework for understanding how CTRs can transport this toxic, yet essential, metal ion across the membrane.


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Product Details
  • ISBN-13: 9781243577238
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 246 mm
  • Weight: 277 gr
  • ISBN-10: 1243577231
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Spine Width: 8 mm
  • Width: 189 mm


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