Molecular structures of the eukaryotic retinal importer ABCA4

  1. Fangyu Liu
  2. James Lee
  3. Jue Chen  Is a corresponding author
  1. The Rockefeller University, United States

Abstract

The ATP-binding cassette (ABC) transporter family contains thousands of members with diverse functions. Movement of the substrate, powered by ATP hydrolysis, can be outward (export) or inward (import). ABCA4 is a eukaryotic importer transporting retinal to the cytosol to enter the visual cycle. It also removes toxic retinoids from the disc lumen to the cytosol. Mutations in ABCA4 cause impaired vision or blindness. Despite decades of clinical, biochemical, and animal model studies, the molecular mechanism of ABCA4 is unknown. Here we report the structures of human ABCA4 in two conformations. In the absence of ATP, ABCA4 adopts an outward-facing conformation, poised to recruit substrate. The presence of ATP induces large conformational changes that could lead to substrate release. These structures provide a molecular basis to understand many disease-causing mutations and a rational guide for new experiments to uncover how ABCA4 recruits, flips, and releases retinoids.

Data availability

The cryo-EM maps are deposited in the Electron Microscopy Data Bank (EMDB) under accession codes: EMD-23409, EMD-23410. The corresponding atomic models are deposited in the Protein Data Bank (PDB) under accession codes 7LKP and 7LKZ.

Article and author information

Author details

  1. Fangyu Liu

    Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5022-0106
  2. James Lee

    Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jue Chen

    Laboratory of Membrane Biophysics and Biology, The Rockefeller University, New York, United States
    For correspondence
    juechen@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2075-4283

Funding

Howard Hughes Medical Institute

  • Jue Chen

Helen Hay Whitney Foundation

  • James Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. David Drew, Stockholm University, Sweden

Publication history

  1. Received: September 28, 2020
  2. Accepted: February 18, 2021
  3. Accepted Manuscript published: February 19, 2021 (version 1)
  4. Version of Record published: March 4, 2021 (version 2)

Copyright

© 2021, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fangyu Liu
  2. James Lee
  3. Jue Chen
(2021)
Molecular structures of the eukaryotic retinal importer ABCA4
eLife 10:e63524.
https://doi.org/10.7554/eLife.63524
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