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TitleStructures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 4339, Year 2022
Publish dateJul 27, 2022
AuthorsPing Li / Amber L Hendricks / Yong Wang / Rhiza Lyne E Villones / Karin Lindkvist-Petersson / Gabriele Meloni / J A Cowan / Kaituo Wang / Pontus Gourdon /
PubMed AbstractIn eukaryotes, iron-sulfur clusters are essential cofactors for numerous physiological processes, but these clusters are primarily biosynthesized in mitochondria. Previous studies suggest ...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.
External linksNat Commun / PubMed:35896548 / PubMed Central
MethodsEM (single particle)
Resolution2.81 - 3.2 Å
Structure data

13606

7pqx

EMDB-13606, PDB-7pqx:
Structure of CtAtm1 in the inward-facing open conformation
Method: EM (single particle) / Resolution: 3.08 Å

13607

7pr1

EMDB-13607, PDB-7pr1:
Structure of CtAtm1 in the occluded conformation with ATP bound
Method: EM (single particle) / Resolution: 2.81 Å

13609

7pro

EMDB-13609, PDB-7pro:
Structure of CtAtm1 in the inward-open with Glutathione-complexed [2Fe-2S] cluster bound
Method: EM (single particle) / Resolution: 3.0 Å

13610

7pru

EMDB-13610, PDB-7pru:
Structure of CtAtm1 in the inward-facing partially occluded with cargo bound
Method: EM (single particle) / Resolution: 3.2 Å

13612

7psd

EMDB-13612, PDB-7psd:
Structure of CtAtm1(E603Q) in the inward-facing open conformation
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-MG:
Unknown entry

ChemComp-GSH:
GLUTATHIONE / Glutathione

Source
  • Chaetomium thermophilum var. thermophilum DSM 1495 (fungus)
  • thermochaetoides thermophila dsm 1495 (fungus)
  • chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
KeywordsMEMBRANE PROTEIN / ABC exporter / transporter

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