TY - JOUR

T1 - Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria

AU - Li, Ping

AU - Hendricks, Amber L.

AU - Wang, Yong

AU - Villones, Rhiza Lyne E.

AU - Lindkvist-Petersson, Karin

AU - Meloni, Gabriele

AU - Cowan, J. A.

AU - Wang, Kaituo

AU - Gourdon, Pontus

PY - 2022

Y1 - 2022

N2 - Mitochondrial Atm1 proteins play important roles in the maturation of certain cytosolic proteins. Here, the authors exploit cryo-EM to capture several structures of an Atm1. The findings shed new light on the molecular function of Atm1 transporters.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 angstrom, 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.

AB - Mitochondrial Atm1 proteins play important roles in the maturation of certain cytosolic proteins. Here, the authors exploit cryo-EM to capture several structures of an Atm1. The findings shed new light on the molecular function of Atm1 transporters.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 angstrom, 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.

KW - IRON-SULFUR CLUSTER

KW - ABC TRANSPORTER ATM1P

KW - GLUTATHIONE

KW - SUBSTRATE

KW - MEMBRANE

KW - PROTEINS

KW - MODEL

KW - LEADS

U2 - 10.1038/s41467-022-32006-8

DO - 10.1038/s41467-022-32006-8

M3 - Journal article

C2 - 35896548

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 4339

ER -