Molecular Organization and ATP-Induced Conformational Changes of ABCA4, the Photoreceptor-Specific ABC Transporter
Open accessAbstract
ATP-binding cassette (ABC) transporters use ATP to translocate various substrates across cellular membranes. Several members of subfamily A of mammalian ABC transporters are associated with severe health disorders, but their unusual complexity and large size have so far precluded structural characterization. ABCA4 is localized to the discs of vertebrate photoreceptor outer segments. This protein transports N-retinylidene-phosphatidylethanolamine to the outer side of disc membranes to prevent formation of toxic compounds causing macular degeneration. An 18 Å-resolution structure of ABCA4 isolated from bovine rod outer segments was determined using electron microscopy and single-particle reconstruction. Significant conformational changes in the cytoplasmic and transmembrane regions were observed upon binding of a nonhydrolyzable ATP analog and accompanied by altered hydrogen/deuterium exchange in the Walker A motif of one of the nucleotide-binding domains. These findings provide an initial view of the molecular organization and functional rearrangements for any member of the ABCA subfamily of ABC transporters.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The structure of native bovine ABCA4 was determined by negative stain electron microscopy to 18 Å resolution.
“The structure of native bovine ABCA4 has been determined by negative stain electron microscopy to a resolution of 18 Å, revealing the overall shape of the molecule.523”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [523]
Conformational changes in ABCA4 have been observed by electron microscopy and hydrogen-deuterium exchange.
“Such conformational changes have indeed been observed by electron microscopy and hydrogen–deuterium exchange.523”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [523]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,260 · see citing works
I-TASSER: a unified platform for automated protein structure and function prediction
Roy, A., Küçükural, A., & Zhang, Y. (2010) · Nature Protocols · doi:10.1038/nprot.2010.5 · Cited by 6,093 · see citing works
ABC Transporters: From Microorganisms to Man
Higgins, C. F. (1992) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.08.110192.000435 · Cited by 3,985 · see citing works
EMAN2: An extensible image processing suite for electron microscopy
Tang, G., Peng, L., Baldwin, P. R., Mann, D. S., Jiang, W., Rees, I., & Ludtke, S. J. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.05.009 · Cited by 2,914 · see citing works
SPIDER and WEB: Processing and Visualization of Images in 3D Electron Microscopy and Related Fields
Frank, J., Radermacher, M., Penczek, P. A., Zhu, J., Li, Y., Ladjadj, M., & Leith, A. G. (1996) · Journal of Structural Biology · doi:10.1006/jsbi.1996.0030 · Cited by 2,026 · see citing works
Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., et al. (2009) · Science · doi:10.1126/science.1168750 · Cited by 1,929 · see citing works
Allikmets, R., Singh, N., Sun, H., Shroyer, N. F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., et al. (1997) · Nature Genetics · doi:10.1038/ng0397-236 · Cited by 1,435 · cited 2× · see citing works
“Mutations in the ABCA4 gene have been linked to devastating visual disorders, such as Stargardt disease , an early onset macular degeneration (Allikmets et al., 1997a; Weleber, 1994), retinitis pigmentosa (Martínez-Mir et al., 1998), cone-rod dystrophy (Hamel, 2007) and a higher susceptibility to…”
BackgroundWeng, J., Mata, N. L., Azarian, S. M., Tzekov, R. T., Birch, D. G., & Travis, G. H. (1999) · Cell · doi:10.1016/s0092-8674(00)80602-9 · Cited by 881 · cited 1× · see citing works
“The main role of ABCA4 is in clearance of alltrans-retinal (ATR), the product of light-induced isomerization of the visual pigment chromophore, 11-cis-retinal, from photoreceptors (Ahn et al., 2000; Maeda et al., 2008; Sun et al., 1999; Weng et al., 1999).”
BackgroundMutation of the Stargardt Disease Gene ( ABCR ) in Age-Related Macular Degeneration
Allikmets, R. L., Shroyer, N. F., Singh, N., Seddon, J. M., Lewis, R. A., Bernstein, P. S., Peiffer, A. P., Zabriskie, N. A., Li, Y., Hutchinson, A. A., et al. (1997) · Science · doi:10.1126/science.277.5333.1805 · Cited by 879 · see citing works
Human ATP-binding cassette (ABC) transporter family
Vasiliou, V., Vasiliou, K., & Nebert, D. W. (2008) · Human Genomics · doi:10.1186/1479-7364-3-3-281 · Cited by 779 · see citing works
Flexibility in the ABC transporter MsbA: Alternating access with a twist
Ward, A. B., Reyes, C. L., Yu, J., Roth, C., & Chang, G. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709388104 · Cited by 774 · see citing works
The ATP switch model for ABC transporters
Higgins, C. F., & Linton, K. J. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb836 · Cited by 752 · see citing works
Holland, I. B., & Blight, M. A. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2993 · Cited by 579 · see citing works
Radermacher, M., Wagenknecht, T., Verschoor, A., & Frank, J. (1987) · Journal of Microscopy · doi:10.1111/j.1365-2818.1987.tb01333.x · Cited by 501 · see citing works
Shaikh, T., Gao, H., Baxter, W., Asturias, F., Boisset, N., Leith, A., & Frank, J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.156 · Cited by 499 · see citing works
Hamel, C. (2007) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-2-7 · Cited by 448 · see citing works
Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR
Martı́nez-Mir, A., Paloma, E., Allikmets, R. L., Ayuso, C., del Río, T., Dean, M. C., Vilageliu, L., Gonzàlez‐Duarte, R., & Balcells, S. (1998) · Nature Genetics · doi:10.1038/ng0198-11 · Cited by 401 · see citing works
Sun, H., Molday, R. S., & Nathans, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8269 · Cited by 353 · see citing works
Self-citationArrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1
Althoff, T., Mills, D. J., Popot, J., & Kühlbrandt, W. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.324 · Cited by 334 · see citing works
The 220-kDa Rim Protein of Retinal Rod Outer Segments Is a Member of the ABC Transporter Superfamily
Illing, M., Molday, L. L., & Molday, R. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.15.10303 · Cited by 304 · see citing works
Self-citationRetinopathy in Mice Induced by Disrupted All-trans-retinal Clearance
Maeda, A., Maeda, T., Golczak, M., & Palczewski, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804505200 · Cited by 300 · see citing works
Self-citationABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer
Quazi, F., Lenevich, S., & Molday, R. S. (2012) · Nature Communications · doi:10.1038/ncomms1927 · Cited by 276 · see citing works
Self-citationABCR expression in foveal cone photoreceptors and its role in Stargardt macular dystrophy
Molday, L. L., Rabin, A. R., & Molday, R. S. (2000) · Nature Genetics · doi:10.1038/77004 · Cited by 269 · see citing works
Self-citationSemi-automated data processing of hydrogen exchange mass spectra using HX-Express
Weis, D. D., Engen, J. R., & Kass, I. J. (2006) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2006.07.025 · Cited by 258 · see citing works
Popot, J., Althoff, T., Bagnard, D., Banères, J., Bazzacco, P., Billon-Denis, E., Catoire, L. J., Champeil, P., Charvolin, D., Cocco, M. J., et al. (2011) · Annual Review of Biophysics · doi:10.1146/annurev-biophys-042910-155219 · Cited by 257 · see citing works
Stargardt's ABCR is localized to the disc membrane of retinal rod outer segments
Sun, H., & Nathans, J. (1997) · Nature Genetics · doi:10.1038/ng0997-15 · Cited by 251 · see citing works
Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation
Hohl, M., Briand, C., Grütter, M. G., & Seeger, M. A. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2267 · Cited by 245 · see citing works
Papermaster, D. S., Schneider, B., Zorn, M., & Kraehenbühl, J. P. (1978) · The Journal of Cell Biology · doi:10.1083/jcb.78.2.415 · Cited by 237 · see citing works
Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography
Nickell, S., Park, P. S.-H., Baumeister, W., & Palczewski, K. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612010 · Cited by 209 · see citing works
Self-citationAleksandrov, L. A., Aleksandrov, A. A., Chang, X.-B., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111713200 · Cited by 208 · see citing works
Fitzgerald, M. L., Morris, A. L., Rhee, J. S., Andersson, L. P., Mendez, A. J., & Freeman, M. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204996200 · Cited by 206 · see citing works
Beharry, S., Zhong, M., & Molday, R. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405216200 · Cited by 174 · see citing works
Self-citationBungert, S., Molday, L. L., & Molday, R. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101902200 · Cited by 173 · see citing works
Self-citationStructural analysis of cloned plasma membrane proteins by freeze-fracture electron microscopy
Eskandari, S., Wright, E. M., Kreman, M., Starace, D. M., & Zampighi, G. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11235 · Cited by 168 · see citing works
Penczek, P. A., Zhu, J., & Frank, J. (1996) · Ultramicroscopy · doi:10.1016/0304-3991(96)00037-x · Cited by 153 · see citing works
Ahn, J., Wong, J. T., & Molday, R. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000555200 · Cited by 130 · see citing works
Self-citationPeelman, F., Labeur, C., Vanloo, B., Roosbeek, S., Devaud, C., Duverger, N., Denèfle, P., Rosier, M., Vandekerckhove, J. S., & Rosseneu, M. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)01105-1 · Cited by 128 · see citing works
Perspectives on the structure–function of ABC transporters: The Switch and Constant Contact Models
George, A. M., & Jones, P. M. (2012) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2012.06.003 · Cited by 124 · see citing works
Dynamics of a bacterial multidrug ABC transporter in the inward- and outward-facing conformations
Mehmood, S., Domene, C., Forest, É., & Jault, J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1204067109 · Cited by 112 · see citing works
Jones, P. M., & George, A. M. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22250 · Cited by 111 · see citing works
Bacteriorhodopsin/Amphipol Complexes: Structural and Functional Properties
Gohon, Y., Dahmane, T., Ruigrok, R. W. H., et al. (2008) · Biophysical Journal · doi:10.1529/biophysj.107.121848 · Cited by 105 · see citing works
The ATP-binding cassette family: a structural perspective
Kos, V. N., & Ford, R. C. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0064-9 · Cited by 100 · see citing works
Projection Structure of P-glycoprotein by Electron Microscopy
Lee, J., Urbatsch, I. L., Senior, A. E., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206871200 · Cited by 80 · see citing works
Papermaster, D. S., Reilly, P., & Schneider, B. G. (1982) · Vision Research · doi:10.1016/0042-6989(82)90204-8 · Cited by 70 · see citing works
Orban, T., Jastrzebska, B., Gupta, S., Wang, B., Miyagi, M., Chance, M. R., & Palczewski, K. (2012) · Structure · doi:10.1016/j.str.2012.03.017 · Cited by 67 · see citing works
Self-citationWeleber, R. G. (1994) · Archives of Ophthalmology · doi:10.1001/archopht.1994.01090180050033 · Cited by 65 · see citing works
A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and Neurodegeneration
Piehler, A. P., Özcürümez, M. K., & Kaminski, W. E. (2012) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2012.00017 · Cited by 53 · see citing works
Ahn, J., Beharry, S., Molday, L. L., & Molday, R. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304236200 · Cited by 48 · see citing works
Self-citationPosttranslational Modifications of the Photoreceptor-Specific ABC Transporter ABCA4
Tsybovsky, Y., Wang, B., Quazi, F., Molday, R. S., & Palczewski, K. (2011) · Biochemistry · doi:10.1021/bi200774w · Cited by 39 · see citing works
Self-citationBiswas, E. E., Kurpad, D. S., Joshi, K., & Biswas, S. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.112896 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Chemistry of the Retinoid (Visual) Cycle
Kiser, P. D., Golczak, M., & Palczewski, K. (2014) · Chemical Reviews · doi:10.1021/cr400107q · Cited by 353 · see citing works
Self-citationRetinoids and Retinal Diseases
Kiser, P. D., & Palczewski, K. (2016) · Annual Review of Vision Science · doi:10.1146/annurev-vision-111815-114407 · Cited by 108 · see citing works
Self-citationStructure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration
Molday, R. S., Garces, F. A., Scortecci, J. F., & Molday, L. L. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.101036 · Cited by 107 · see citing works
Self-citationNano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition
Sander, C. L., Sears, A. E., Pinto, A. F. M., Choi, E. H., Kahremany, S., Gao, F., Salom, D., Jin, H., Pardon, E., Suh, S., et al. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202101063 · Cited by 36 · see citing works
Self-citation
- Authors
- Tsybovsky, Y., Orban, T., Molday, R. S., Taylor, D., & Palczewski, K.
- Affiliations
- Case Western Reserve University (US)
- University of British Columbia (CA)
- Corresponding author
- Tsybovsky, Yaroslav
- Palczewski, Krzysztof
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 21
- Issue
- 5
- Pages
- 854-860
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC3654078
- OpenAlex
- W2154057556
- Cited by
- 53
- References
- 50
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 9 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 10 · 2013: 5
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canada Research Chairs
- National Eye Institute (EY021126, EY009339, R24EY021126, EY002422, R01EY002422, R01EY009339)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- ABCA4, ABC transporters, photoreceptor outer segments, macular degeneration, transporter structure, conformational change, nonhydrolyzable ATP analog, Walker A motif, hydrogen-deuterium exchange, rod outer segments
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Cattle, Hydrolysis, Molecular Sequence Data, Rod Cell Outer Segment, Protein Structure, Tertiary, ATP-Binding Cassette Transporters
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
