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| Title | Cryo-EM structures of Cdr1 reveal snapshots of substrate transport and diverse inhibitor recognition. |
|---|---|
| Journal, issue, pages | Sci Adv, Vol. 12, Issue 35, Page eaef7706, Year 2026 |
| Publish date | Aug 28, 2026 |
Authors | Zhen Wang / Shuting Yang / Binyu Zhang / Hengyi Jiang / Yinxia Li / Rongchao Gao / Yulong Wang / Fengying Fan / Lili Dong / Jiaxuan Qiu / Xiurui Li / Yue Zhou / Alastair I H Murchie / Xuekui Yu / ![]() |
| PubMed Abstract | In -a World Health Organization fungal priority pathogen-overexpression of the adenosine triphosphate (ATP)-binding cassette transporter Cdr1 drives multidrug resistance. We present seven cryo- ...In -a World Health Organization fungal priority pathogen-overexpression of the adenosine triphosphate (ATP)-binding cassette transporter Cdr1 drives multidrug resistance. We present seven cryo-electron microscopy structures capturing substrate entry and expulsion. An inward-facing transmembrane channel with three on-off substrate binding sites defines a proposed entry pathway for a single substrate molecule. Coordinated ATP binding to both nucleotide-binding domains induces transmembrane domain closure, driving the substrate expulsion; adenosine diphosphate release following ATP hydrolysis resets the transporter to an inward-open conformation, enabling substrate entry for the next translocation cycle. Structures with three structurally diverse inhibitors resolve two distinct binding modes: one occupying all three substrate sites and another specifically binding two extracellular-proximal sites. These findings provide snapshots of the substrate translocation cycle and structural blueprints for antifungal drug design. |
External links | Sci Adv / PubMed:42664345 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.41 - 2.95 Å |
| Structure data | EMDB-65307, PDB-9vsu: EMDB-65308, PDB-9vsv: EMDB-65309, PDB-9vsw: EMDB-65311, PDB-9vsz: EMDB-65312, PDB-9vt1: EMDB-65313, PDB-9vt2: EMDB-65335, PDB-9vtm: EMDB-65336, PDB-9vtn: EMDB-65337, PDB-9vto: EMDB-68246, PDB-22fr: |
| Chemicals | ![]() ChemComp-FK5: ![]() ChemComp-CC9: ![]() ChemComp-TPF: ![]() ChemComp-MG: ![]() ChemComp-ADP: ![]() ChemComp-ATP: ![]() ChemComp-HOH: ![]() ChemComp-ANP: |
| Source |
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Keywords | MEMBRANE PROTEIN / Candida albicans / Multidrug resistance / Substrate efflux cycle / TRANSPORT PROTEIN / Inhibitor |
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candida albicans sc5314 (yeast)
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