Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Iron-sulfur clusters are crucial cofactors for many eukaryotic physiological processes.
• Mitochondria are the primary sites for iron-sulfur cluster biosynthesis.
• The role of mitochondrial ABCB7-type exporters in cytosolic iron-sulfur protein maturation is suggested but mechanistically unclear.

Purpose of the Study:

• To elucidate the molecular mechanism of eukaryotic ABCB7-type exporters in iron-sulfur cluster transport.
• To characterize the structure and function of CtAtm1, a eukaryotic homolog of human ABCB7.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine high-resolution structures of CtAtm1.
• Functional characterization of CtAtm1.
• In silico molecular docking.

Main Results:

• A series of cryo-EM structures of CtAtm1 were determined at resolutions of 2.8–3.2 Å.
• A model for CtAtm1 accepting glutathione-complexed iron-sulfur clusters was proposed.
• Structural intermediates, including partially and early occluded states, were identified, revealing cargo-binding and internalization mechanisms.

Conclusions:

• The findings provide significant insights into the transport mechanism of eukaryotic ABCB7-type proteins.
• The study proposes a model for how CtAtm1 facilitates the transfer of iron-sulfur clusters.
• This work advances the understanding of essential cofactor transport in eukaryotes.