Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

The structural characterization of Cytochrome c oxidase assembly factor 6 (Coa6) (#301)

Shadi Maghoolpilehrood 1 , Dinesha Cooray 2 , David Aragão 3 , David Stroud 4 , Michael T Ryan 4 , Megan Maher 1
  1. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne
  2. La Trobe University, Bundoora, VIC, Australia
  3. Australian Synchrotron, Clayton, Melbourne
  4. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Melbourne

Copper is a crucial trace element required by all living organisms, particularly humans where it is important as an active cofactor in a wide range of biological processes such as mitochondrial respiration. Despite the vitality of copper in living organisms, even low levels of free copper are highly toxic to the cell and need to be complexed intracellularly. Therefore intracellular copper trafficking, especially the Cu trafficking to and within the mitochondria is a crucial process. The enzyme cytochrome c oxidase (CcO), which is the terminal oxidase of the mitochondrial respiratory chain requires copper as an essential cofactor. The assembly of dinuclear CuA and mononuclear CuB sites are critical for the activity of the complex.

Recently, it has been suggested that Coa6, a protein located in the intermembrane space of mitochondria, is involved in the Cu-delivery pathway to CcO [1]. Recent work has shown that Coa6 binds Cu(I) with Kd ~10-17 M [2]. Despite in vivo studies having characterized the interactions between the Coa6 and other proteins involved in mitochondrial copper homeostasis, including subunits of CcO, the mechanism by which Coa6 plays a role in CcO assembly remains unknown.

This poster will describe the expression, purification and the crystal structure of the Coa6 protein.

  1. [1] Vogtle FN et al., Mol. Cell. Proteomics, 2012, 11, 1840-52. [2] Stroud DA et al., Hum. Mol. Gen., 2015, 24, 5404-15