ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer
Open accessAbstract
It has been proposed that the reaction cycle of ATP binding cassette (ABC) transporters is driven by dimerization of their ABC motor domains upon binding ATP at their mutual interface. However, no such ATP sandwich complex has been observed for an ABC from an ABC transporter. In this paper, we report the crystal structure of a stable dimer formed by the E171Q mutant of the MJ0796 ABC, which is hydrolytically inactive due to mutation of the catalytic base. The structure shows a symmetrical dimer in which two ATP molecules are each sandwiched between the Walker A motif in one subunit and the LSGGQ signature motif in the other subunit. These results establish the stereochemical basis of the power stroke of ABC transporter pumps.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Further work demonstrated the role of the Walker A and B motifs in forming the ATP bindings site sandwich required for homodimerization of the ALD protein, and the subsequent power stroke of ATP-dependent substrate transport.
“Further work demonstrated the role of the Walker A and B motifs in forming the ATP bindings site sandwich required for homodimerization of the ALD protein, and the subsequent power stroke of ATP-dependent substrate transport [36,37].”
From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [37]
Cited by
Sorted by citations
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761 · see citing works
Prokaryotic Nucleotide Excision Repair: The UvrABC System
Truglio, J. J., Croteau, D. L., Van Houten, B., & Kisker, C. (2006) · Chemical Reviews · doi:10.1021/cr040471u · Cited by 340 · see citing works
Prokaryotic Nucleotide Excision Repair
Kisker, C., Kuper, J., & Van Houten, B. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012591 · Cited by 192 · see citing works
Genovese, I., Ilari, A., Assaraf, Y. G., Fazi, F., & Colotti, G. (2017) · Drug Resistance Updates · doi:10.1016/j.drup.2017.10.003 · Cited by 156 · see citing works
Advances in the Mass Spectrometry of Membrane Proteins: From Individual Proteins to Intact Complexes
Barrera, N. P., & Robinson, C. V. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062309-093307 · Cited by 154 · see citing works
Ernst, R., Kueppers, P., Klein, C. M., Schwarzmueller, T., Kuchler, K., & Schmitt, L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800191105 · Cited by 146 · see citing works
Comparison of mechanistic transport cycle models of ABC exporters
Szöllősi, D., Rose-Sperling, D., Hellmich, U. A., & Stockner, T. (2018) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2017.10.028 · Cited by 107 · see citing works
Structure 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
Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration
Molday, R. S., & Zhang, K. (2010) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.07.002 · Cited by 82 · see citing works
“These include an A-loop with a conserved aromatic amino acid (phenylalanine in NBD1 and tyrosine in NBD2) involved in stacking interactions with the adenine ring of ATP [106,107], flexible Q-loop containing a conserved glutamine and involved in the transmission of conformational changes between the NBDs and the TMD [1…”
BackgroundKawaguchi, K., & Morita, M. (2016) · BioMed Research International · doi:10.1155/2016/6786245 · Cited by 81 · see citing works
Mallack, E. J., Gao, K., Engelen, M., & Kemp, S. (2022) · Cells · doi:10.3390/cells11020283 · Cited by 60 · see citing works
“Further work demonstrated the role of the Walker A and B motifs in forming the ATP bindings site sandwich required for homodimerization of the ALD protein, and the subsequent power stroke of ATP-dependent substrate transport [36,37].”
BackgroundWada, S.-I., Tanabe, K., Yamazaki, A., Niimi, M., Uehara, Y., Niimi, K., Lamping, E., Cannon, R. D., & Monk, B. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408252200 · Cited by 39 · see citing works
- Authors
- Smith, P. C., Karpowich, N., Millen, L., Moody, J. E., Rosen, J., Thomas, P. J., & Hunt, J. F.
- Affiliations
- Columbia University (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Hunt, John F
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 10
- Issue
- 1
- Pages
- 139-149
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3516284
- OpenAlex
- W2072135452
- Cited by
- 773
- References
- 0
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 16 · 2021: 16 · 2020: 36 · 2019: 21 · 2018: 28 · 2017: 18 · 2016: 19 · 2015: 25 · 2014: 36 · 2013: 28 · 2012: 30
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049835)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- ABC transporters, ATP binding, Walker A motif, power stroke, ATP hydrolysis, crystal structure
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Allosteric Regulation, Amino Acid Sequence, Binding Sites, Fluorescence Polarization, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Sodium, Methanococcus, Protein Structure, Tertiary, Crystallography, X-Ray, ATP-Binding Cassette Transporters, Dimerization, Molecular Motor Proteins, Amino Acid Motifs, Static Electricity
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
