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TitleConformational cycle and small-molecule inhibition mechanism of a plant ABCB transporter in lipid membranes.
Journal, issue, pagesSci Adv, Vol. 11, Issue 24, Page eadv9721, Year 2025
Publish dateJun 13, 2025
AuthorsYong Liu / Maofu Liao /
PubMed AbstractIn plants, ATP-binding cassette (ABC) transporters are crucial for nutrient uptake, phytohormone transport, and environmental response. It is of great interest to understand the mechanisms of these ...In plants, ATP-binding cassette (ABC) transporters are crucial for nutrient uptake, phytohormone transport, and environmental response. It is of great interest to understand the mechanisms of these transporters and develop small-molecule modulators to regulate plant growth. ABCB19 was recently shown to transport brassinosteroid, shaping hormone dynamics and plant architecture. However, the conformational cycle and inhibitor mechanism of ABCB transporters remain elusive. We reconstituted ABCB19 into lipid nanodiscs, where activity was drastically higher than in detergents, and determined its cryo-electron microscopy structures in substrate-free, substrate-bound, vanadate-trapped, and inhibitor-bound states. Inward-facing ABCB19 moved inward upon substrate binding and fully closed with vanadate trapping, unexpectedly temperature dependent. Two inhibitor molecules locked ABCB19 in the inward-facing conformation. Mutagenesis identified key residues for substrate and inhibitor binding, revealing differential contributions to transporter function and inhibition. These results deepen knowledge of plant ABCB transporters, laying a foundation for targeted manipulation to enhance plant resilience and productivity.
External linksSci Adv / PubMed:40512840 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 4.1 Å
Structure data

EMDB-62306, PDB-9kg2:
Cryo-EM structure of apo form atABCB19 in lipid nanodisc
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-62366, PDB-9kjc:
Cryo-EM structure of BL-bound atABCB19 in lipid nanodisc
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-62383, PDB-9kk6:
Cryo-EM structure of vanadate-trapped atABCB19 in lipid nanodisc
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-62385, PDB-9kke:
Cryo-EM structure of BUM-bound atABCB19 in lipid nanodisc
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-BLD:
Brassinolide / hormone*YM

ChemComp-VO4:
VANADATE ION

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

PDB-1efv:
THREE-DIMENSIONAL STRUCTURE OF HUMAN ELECTRON TRANSFER FLAVOPROTEIN TO 2.1 A RESOLUTION

Source
  • arabidopsis thaliana (thale cress)
  • arabidopsis thaliana x arabidopsis lyrata (thale cress)
KeywordsMEMBRANE PROTEIN / ABCB19 / Plant hormone transport / apo form / BL-bound / vandate-trapped / BUM-bound

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