ArticleNature communications2021
Structural basis of substrate recognition and translocation by human ABCA4.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- In Silico Prioritization of Variants of Uncertain Significance in ABCA4 Reveals Conserved Functional Motifs.Research square · 2026Article
- Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.Stem cells (Dayton, Ohio) · 2026Article
- Lipid transport mechanisms in human ABCA family transporters: a structural perspective.Biochemical Society transactions · 2026Review
- Adenosine triphosphate-binding cassette transporters: key players in maintaining fetal health during pregnancy.Frontiers in endocrinology · 2026Review
- Cryo-EM analysis of the Staphylococcus aureus phenol-soluble modulin exporter PmtCD apo form in detergent micelles, nanodiscs and peptidiscs.Communications biology · 2025Article
- Retinoid dynamics in vision: from visual cycle biology to retina disease treatments.Pharmacology & therapeutics · 2025Review
- Generation of a compound heterozygous ABCA4 rat model with pathological features of STGD1.Human molecular genetics · 2025Article
- Genome-wide identification analysis of the ATP-binding cassette transporter family and expression analysis under methyl jasmonate treatment in Panax ginseng.BMC plant biology · 2025Article
- Cryo-EM analyses unveil details of mechanism and targocil-II mediated inhibition of S. aureus WTA transporter TarGH.Nature communications · 2025Article
- Activation of GSDME by all-International journal of biological sciences · 2025Article
- Exploring the Role of ABCA4's ECD2 Domain in Inherited Retinal Degeneration: Computational and Functional Perspectives.Advances in experimental medicine and biology · 2025Article
- Assessment of ABCA4 Genetic Variants: Current Landscape and Future Prospects.Advances in experimental medicine and biology · 2025Review
- Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.Advances in protein chemistry and structural biology · 2025Review
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- The central retinal thickness and its related genotype in ABCA4-related retinopathy.Eye (London, England) · 2024Article
- Cryo-EM structures of a mycobacterial ABC transporter that mediates rifampicin resistance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The ABC's of Alzheimer risk gene ABCA7.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Identification and expression analysis of ATP-binding cassette (ABC) transporters revealed its role in regulating stress response in pear (Pyrus bretchneideri).BMC genomics · 2024Article
- Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.Nature communications · 2024Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across the membrane. Mutations in human ABCA transporters have been described to cause severe hereditary disorders associated with impaired lipid transport. However, little is known about the mechanistic details of substrate recognition and translocation by ABCA transporters. Here, we present three cryo-EM structures of human ABCA4, a retina-specific ABCA transporter, in distinct functional states at resolutions of 3.3-3.4 Å. In the nucleotide-free state, the two transmembrane domains (TMDs) exhibit a lateral-opening conformation, allowing the lateral entry of substrate from the lipid bilayer. The N-retinylidene-phosphatidylethanolamine (NRPE), the physiological lipid substrate of ABCA4, is sandwiched between the two TMDs in the luminal leaflet and is further stabilized by an extended loop from extracellular domain 1. In the ATP-bound state, the two TMDs display a closed conformation, which precludes the substrate binding. Our study provides a molecular basis to understand the mechanism of ABCA4-mediated NRPE recognition and translocation, and suggests a common 'lateral access and extrusion' mechanism for ABCA-mediated lipid transport.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.