EMD-28047
Cryo-EM Structure of human ABCA7 in PE/Ch nanodiscs
EMD-28047
Single-particle4.0 Å
Deposition: 06/09/2022Map released: 21/12/2022
Last modified: 30/10/2024
Sample Organism:
Homo sapiens
Sample: Human ABCA7 in Porcine BPL/Ch/MSP1D1 nanodiscs
Fitted models: 8ee6 (Avg. Q-score: 0.314)
Deposition Authors: Alam A
,
Le LTM ,
Thompson JR
Sample: Human ABCA7 in Porcine BPL/Ch/MSP1D1 nanodiscs
Fitted models: 8ee6 (Avg. Q-score: 0.314)
Deposition Authors: Alam A
,
Le LTM ,
Thompson JR
Cryo-EM structures of human ABCA7 provide insights into its phospholipid translocation mechanisms.
Le LTM ,
Thompson JR ,
Dehghani-Ghahnaviyeh S ,
Pant S,
Dang PX,
French JB ,
Kanikeyo T ,
Tajkhorshid E ,
Alam A
(2023) EMBO J , 42 , e111065 - e111065
,
Thompson JR ,
Dehghani-Ghahnaviyeh S ,
Pant S,
Dang PX,
French JB ,
Kanikeyo T ,
Tajkhorshid E ,
Alam A
(2023) EMBO J , 42 , e111065 - e111065
Abstract:
Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and in a nucleotide-bound, closed state at resolutions between 3.6 and 4.0 Å. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.
Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and in a nucleotide-bound, closed state at resolutions between 3.6 and 4.0 Å. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.