Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria
(2022) In Nature Communications 13(1).- Abstract
In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here, we report a series of cryo-electron microscopy structures of a eukaryotic homolog of human ABCB7, CtAtm1, determined at average resolutions ranging from 2.8 to 3.2 Å, complemented by functional characterization and molecular docking in silico. We propose that CtAtm1 accepts delivery from glutathione-complexed iron-sulfur clusters. A partially... (More)
In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here, we report a series of cryo-electron microscopy structures of a eukaryotic homolog of human ABCB7, CtAtm1, determined at average resolutions ranging from 2.8 to 3.2 Å, complemented by functional characterization and molecular docking in silico. We propose that CtAtm1 accepts delivery from glutathione-complexed iron-sulfur clusters. A partially occluded state links cargo-binding to residues at the mitochondrial matrix interface that line a positively charged cavity, while the binding region becomes internalized and is partially divided in an early occluded state. Collectively, our findings substantially increase the understanding of the transport mechanism of eukaryotic ABCB7-type proteins.
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- author
- Li, Ping LU ; Hendricks, Amber L. ; Wang, Yong ; Villones, Rhiza Lyne E. ; Lindkvist-Petersson, Karin LU ; Meloni, Gabriele ; Cowan, J. A. ; Wang, Kaituo and Gourdon, Pontus LU
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- article number
- 4339
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85135072772
- pmid:35896548
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-022-32006-8
- language
- English
- LU publication?
- yes
- id
- 0953f345-56be-4cd8-a955-457c3035d6a7
- date added to LUP
- 2022-10-11 14:00:36
- date last changed
- 2024-12-13 10:47:08
@article{0953f345-56be-4cd8-a955-457c3035d6a7,
abstract = {{<p>In eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest mitochondrial ABCB7-type exporters are involved in maturation of cytosolic iron-sulfur proteins. However, the molecular mechanism for how the ABCB7-type exporters participate in this process remains elusive. Here, we report a series of cryo-electron microscopy structures of a eukaryotic homolog of human ABCB7, CtAtm1, determined at average resolutions ranging from 2.8 to 3.2 Å, complemented by functional characterization and molecular docking in silico. We propose that CtAtm1 accepts delivery from glutathione-complexed iron-sulfur clusters. A partially occluded state links cargo-binding to residues at the mitochondrial matrix interface that line a positively charged cavity, while the binding region becomes internalized and is partially divided in an early occluded state. Collectively, our findings substantially increase the understanding of the transport mechanism of eukaryotic ABCB7-type proteins.</p>}},
author = {{Li, Ping and Hendricks, Amber L. and Wang, Yong and Villones, Rhiza Lyne E. and Lindkvist-Petersson, Karin and Meloni, Gabriele and Cowan, J. A. and Wang, Kaituo and Gourdon, Pontus}},
issn = {{2041-1723}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria}},
url = {{http://dx.doi.org/10.1038/s41467-022-32006-8}},
doi = {{10.1038/s41467-022-32006-8}},
volume = {{13}},
year = {{2022}},
}