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The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron

Karlberg, Tobias LU ; Schagerlöf, Ulrika LU ; Gakh, Oleksandr ; Park, Sungjo ; Ryde, Ulf LU orcid ; Lindahl, Martin LU ; Leath, Kirstin ; Garman, Elspeth ; Isaya, Grazia and Al-Karadaghi, Salam LU (2006) In Structure 14(10). p.1535-1546
Abstract
Defects in the mitochondrial protein frataxin are responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children. Here, we present the crystal structures of the iron-free and iron-loaded frataxin trimers, and a single-particle electron microscopy reconstruction of a 24 subunit oligomer. The structures reveal fundamental aspects of the frataxin mechanism. The trimer has a central channel in which one atom of iron binds. Two conformations of the channel with different metal-binding affinities suggest that a gating mechanism controls whether the bound iron is delivered to other proteins or transferred to detoxification sites. The trimer constitutes the basic structural unit of the 24 subunit... (More)
Defects in the mitochondrial protein frataxin are responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children. Here, we present the crystal structures of the iron-free and iron-loaded frataxin trimers, and a single-particle electron microscopy reconstruction of a 24 subunit oligomer. The structures reveal fundamental aspects of the frataxin mechanism. The trimer has a central channel in which one atom of iron binds. Two conformations of the channel with different metal-binding affinities suggest that a gating mechanism controls whether the bound iron is delivered to other proteins or transferred to detoxification sites. The trimer constitutes the basic structural unit of the 24 subunit oligomer. The architecture of this oligomer and several features of the trimer structure demonstrate striking similarities to the iron-storage protein ferritin. The data reveal how stepwise assembly provides frataxin with the structural flexibility to perform two functions: metal delivery and detoxification. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Structure
volume
14
issue
10
pages
1535 - 1546
publisher
Cell Press
external identifiers
  • wos:000241241800007
  • scopus:33749265843
ISSN
0969-2126
DOI
10.1016/j.str.2006.08.010
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039), Biochemistry and Structural Biology (S) (000006142)
id
9bf02057-70c8-4b8e-9a09-5b6cc75ac734 (old id 387207)
alternative location
http://www.structure.org/content/article/abstract?uid=PIIS0969212606003601
date added to LUP
2016-04-01 12:30:07
date last changed
2021-09-22 02:42:22
@article{9bf02057-70c8-4b8e-9a09-5b6cc75ac734,
  abstract     = {Defects in the mitochondrial protein frataxin are responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children. Here, we present the crystal structures of the iron-free and iron-loaded frataxin trimers, and a single-particle electron microscopy reconstruction of a 24 subunit oligomer. The structures reveal fundamental aspects of the frataxin mechanism. The trimer has a central channel in which one atom of iron binds. Two conformations of the channel with different metal-binding affinities suggest that a gating mechanism controls whether the bound iron is delivered to other proteins or transferred to detoxification sites. The trimer constitutes the basic structural unit of the 24 subunit oligomer. The architecture of this oligomer and several features of the trimer structure demonstrate striking similarities to the iron-storage protein ferritin. The data reveal how stepwise assembly provides frataxin with the structural flexibility to perform two functions: metal delivery and detoxification.},
  author       = {Karlberg, Tobias and Schagerlöf, Ulrika and Gakh, Oleksandr and Park, Sungjo and Ryde, Ulf and Lindahl, Martin and Leath, Kirstin and Garman, Elspeth and Isaya, Grazia and Al-Karadaghi, Salam},
  issn         = {0969-2126},
  language     = {eng},
  number       = {10},
  pages        = {1535--1546},
  publisher    = {Cell Press},
  series       = {Structure},
  title        = {The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron},
  url          = {http://dx.doi.org/10.1016/j.str.2006.08.010},
  doi          = {10.1016/j.str.2006.08.010},
  volume       = {14},
  year         = {2006},
}