The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake
Abstract The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformatio...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55136-7 |
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| author | Imre Gonda Simona Sorrentino Laura Galazzo Nicolas P. Lichti Fabian M. Arnold Ahmad R. Mehdipour Enrica Bordignon Markus A. Seeger |
| author_facet | Imre Gonda Simona Sorrentino Laura Galazzo Nicolas P. Lichti Fabian M. Arnold Ahmad R. Mehdipour Enrica Bordignon Markus A. Seeger |
| author_sort | Imre Gonda |
| collection | DOAJ |
| description | Abstract The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformation, but does not sample an outward-facing conformation. When IrtAB is locked in its outward-occluded conformation in nanodiscs, mycobactin is bound in the middle of the lipid bilayer at a membrane-facing crevice opening at the heterodimeric interface. Mutations introduced at the crevice abrogate mycobactin import and in corresponding structures, the crevice is collapsed. A conserved triple histidine motif coordinating a zinc ion is present below the mycobactin binding site. Substitution of these histidine residues with alanine results in a decoupled transporter, which hydrolyzes ATP, but lost its capacity to import mycobactins. Our data suggest that IrtAB imports mycobactin via a credit-card mechanism in a transport cycle that is coupled to the presence of zinc. |
| format | Article |
| id | doaj-art-35233daa677d4cbb954703fb410869c7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-35233daa677d4cbb954703fb410869c72025-02-02T12:33:08ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-024-55136-7The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptakeImre Gonda0Simona Sorrentino1Laura Galazzo2Nicolas P. Lichti3Fabian M. Arnold4Ahmad R. Mehdipour5Enrica Bordignon6Markus A. Seeger7Institute of Medical Microbiology, University of ZurichCenter for Microscopy and Image Analysis, University of ZurichDepartment of Physical Chemistry, University of GenevaInstitute of Medical Microbiology, University of ZurichInstitute of Medical Microbiology, University of ZurichUGent Center for Molecular Modelling, Ghent UniversityDepartment of Physical Chemistry, University of GenevaInstitute of Medical Microbiology, University of ZurichAbstract The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformation, but does not sample an outward-facing conformation. When IrtAB is locked in its outward-occluded conformation in nanodiscs, mycobactin is bound in the middle of the lipid bilayer at a membrane-facing crevice opening at the heterodimeric interface. Mutations introduced at the crevice abrogate mycobactin import and in corresponding structures, the crevice is collapsed. A conserved triple histidine motif coordinating a zinc ion is present below the mycobactin binding site. Substitution of these histidine residues with alanine results in a decoupled transporter, which hydrolyzes ATP, but lost its capacity to import mycobactins. Our data suggest that IrtAB imports mycobactin via a credit-card mechanism in a transport cycle that is coupled to the presence of zinc.https://doi.org/10.1038/s41467-024-55136-7 |
| spellingShingle | Imre Gonda Simona Sorrentino Laura Galazzo Nicolas P. Lichti Fabian M. Arnold Ahmad R. Mehdipour Enrica Bordignon Markus A. Seeger The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake Nature Communications |
| title | The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake |
| title_full | The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake |
| title_fullStr | The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake |
| title_full_unstemmed | The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake |
| title_short | The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake |
| title_sort | mycobacterial abc transporter irtab employs a membrane facing crevice for siderophore mediated iron uptake |
| url | https://doi.org/10.1038/s41467-024-55136-7 |
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