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Structural Basis of Glutathione Recognition by the Yeast Cadmium Factor 1.

ABSTRACT: Transporters from the ABCC family have an essential role in detoxifying electrophilic compounds including metals, drugs, and lipids, often through conjugation with glutathione complexes. The yeast cadmium factor 1 (Ycf1), plays such a role in yeast, and can transport glutathione alone as well as conjugate to toxic heavy metals including Cd²⁺, Hg²⁺, and As³⁺. To understand the complicated pleiotropy of heavy metal substrate binding, we determined the cryo-EM structure of Ycf1 bound to the substrate, oxidized glutathione, and performed cellular survival assays against heavy metals to determine the basis for pleiotropic binding that adapts to different-sized metal complexes. We identify a "flex-pocket" for substrate binding that binds glutathione complexes asymmetrically and flexes to accommodate different size complexes.

SUBMITTER: Soong TH

PROVIDER: S-EPMC10862839 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Structural Basis for Oxidized Glutathione Recognition by the Yeast Cadmium Factor 1.

Soong Tik Hang TH Hotze Clare C Khandelwal Nitesh Kumar NK Tomasiak Thomas M TM

bioRxiv : the preprint server for biology 20240326

Transporters from the ABCC family have an essential role in detoxifying electrophilic compounds including metals, drugs, and lipids, often through conjugation with glutathione complexes. The Yeast Cadmium Factor 1 (Ycf1) transports glutathione alone as well as glutathione conjugated to toxic heavy metals including Cd2+, Hg2+, and As3+. To understand the complicated selectivity and promiscuity of heavy metal substrate binding, we determined the cryo-EM structure o ...[more]

PMID: 38352558

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