The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome
Open accessPublished version of a preprint
Abstract
The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.
Overview
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
Verification
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“P320 in PSMC5 is located outside of the AAA ATPase domain (Fig. 3C) and at the interface of the 19S RP and the 20S CP [34] (Fig. 3D).”
From PSMC5 insufficiency and P320R mutation impair proteasome function (2024) · cites this paper as [34]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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 46,047
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
Inference of Macromolecular Assemblies from Crystalline State
Krissinel, E., & Henrick, K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.05.022 · Cited by 10,007
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S. Q., Palovcak, E. J., Armache, J., Verba, K. A., Cheng, Y., & Agard, D. A. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,496
PHENIX: a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkòczi, G., Chen, V. B., Davis, I., Echols, N., Headd, J. J., Hung, L., Kapral, G. J., Grosse‐Kunstleve, R. W., et al. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334
Automated electron microscope tomography using robust prediction of specimen movements
Mastronarde, D. N. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.07.007 · Cited by 5,136
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,417
Structure of 20S proteasome from yeast at 2.4Å resolution
Groll, M., Ditzel, L., Löwe, J., Stock, D., Bochtler, M., Bartunik, H. D., & Huber, R. (1997) · Nature · doi:10.1038/386463a0 · Cited by 2,265
Cited by
Sorted by citations
An expanded lexicon for the ubiquitin code
Đikić, I., & Schulman, B. A. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00543-1 · Cited by 426
Antigen presentation in cancer — mechanisms and clinical implications for immunotherapy
Yang, K., Halima, A., & Chan, T. A.-T. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00789-4 · Cited by 352
Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding
Twomey, E. C., Ji, Z., Wales, T. E., Bodnar, N. O., Ficarro, S. B., Marto, J. A., Engen, J. R., & Rapoport, T. A. (2019) · Science · doi:10.1126/science.aax1033 · Cited by 293
Functional Modules of the Proteostasis NetworkPreprint
Jayaraj, G. G., Hipp, M. S., & Hartl, F. U. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033951 · Cited by 254
The molecular principles governing the activity and functional diversity of AAA+ proteins
Puchades, C., Sandate, C. R., & Lander, G. C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0183-6 · Cited by 239
Metadata
- Authors
- Dong, Y., Zhang, S., Wu, Z., Li, X., Wang, W. L., Zhu, Y., Stoilova-McPhie, S., Lu, Y., Finley, D., & Mao, Y.
- Affiliations
- Harvard University (US)
- Peking University (CN)
- Corresponding author
- Mao, Youdong
- ORCID
- Venue
- Nature
- Published
- 2018-11-12
- Volume
- 565
- Issue
- 7737
- Pages
- 49-55
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6370054
- OpenAlex
- W2900290772
- Cited by
- 328
- References
- 77
- Citations by year
- 2026: 27 · 2025: 47 · 2024: 30 · 2023: 36 · 2022: 44 · 2021: 46 · 2020: 49 · 2019: 48
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (1541959)
- Harvard University (1541959)
- National Natural Science Foundation of China (11774012, 91530321)
- Peking University
- Recruitment Program of Global Experts
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM043601, R37GM043601)
- National Institute of Allergy and Infectious Diseases (UM1AI100645)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- 26S proteasome, ATP hydrolysis, substrate translocation, deubiquitination, ubiquitin recognition, protein unfolding
- MeSH terms
- Adenosine Triphosphatases, Adenosine Triphosphate, Allosteric Regulation, Humans, Hydrolysis, Models, Molecular, Protein Conformation, Substrate Specificity, Holoenzymes, Cryoelectron Microscopy, Protein Structure, Quaternary, Proteasome Endopeptidase Complex, Ubiquitination, Protein Unfolding
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
