Structural Basis for Oxidized Glutathione Recognition by the Yeast Cadmium Factor 1.
bioRxiv
; 2024 Mar 26.
Article
em En
| MEDLINE
| ID: mdl-38352558
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) 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 of Ycf1 bound to the substrate, oxidized glutathione. We systematically tested binding determinants with cellular survival assays against cadmium to determine how the substrate site accommodates different-sized metal complexes. We identify a "flex-pocket" for substrate binding that binds glutathione complexes asymmetrically and flexes to accommodate different size complexes.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos