Jump to main content
Jump to site search

Issue 6, 2017
Previous Article Next Article

Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe–S cluster assembly centers

Author affiliations

Abstract

Early studies of the bacterial Fe–S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe–S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1. Here, in the absence of Yfh1, Isu1 was found to exist in two forms, one mostly monomeric with limited tendency to dimerize, and one with a strong propensity to oligomerize. Whereas the monomeric form is stabilized by zinc, the loss of zinc promotes formation of dimer and higher order oligomers. However, upon binding to oligomeric Yfh1, both forms take on a similar symmetrical trimeric configuration that places the Fe–S cluster coordinating residues of Isu1 in close proximity of iron-binding residues of Yfh1. This configuration is suitable for docking of Nfs1 in a manner that provides a structural context for coordinate iron and sulfur donation to the scaffold. Moreover, distinct structural features suggest that in physiological conditions the zinc-regulated abundance of monomeric vs. oligomeric Isu1 yields [Yfh1]·[Isu1] complexes with different Isu1 configurations that afford unique functional properties for Fe–S cluster assembly and delivery.

Graphical abstract: Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe–S cluster assembly centers

Back to tab navigation

Supplementary files

Publication details

The article was received on 28 Mar 2017, accepted on 02 May 2017 and first published on 26 May 2017


Article type: Paper
DOI: 10.1039/C7MT00089H
Citation: Metallomics, 2017,9, 773-801
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe–S cluster assembly centers

    B. K. Galeano, W. Ranatunga, O. Gakh, D. Y. Smith, J. R. Thompson and G. Isaya, Metallomics, 2017, 9, 773
    DOI: 10.1039/C7MT00089H

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements