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
; 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/387207
- author
- Karlberg, Tobias
LU
; Schagerlöf, Ulrika
LU
; Gakh, Oleksandr
; Park, Sungjo
; Ryde, Ulf
LU
; Lindahl, Martin
LU
; Leath, Kirstin
; Garman, Elspeth
; Isaya, Grazia
and Al-Karadaghi, Salam
LU
- organization
- publishing date
- 2006
- 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
- 2023-01-24 02:30:29
@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 = {{https://lup.lub.lu.se/search/files/135493734/88_frataxin.pdf}},
doi = {{10.1016/j.str.2006.08.010}},
volume = {{14}},
year = {{2006}},
}