Chaperone-Bound Clients: The Importance of Being Dynamic
Open accessAbstract
Several recent atomic-resolution studies have resolved how chaperones interact with their client proteins. In some cases, molecular chaperones recognize and bind their clients in conformational ensembles that are locally highly dynamic and interconvert, while in other cases clients bind in unique conformations. The presence of a locally dynamic client ensemble state has important consequences, both for the interpretation of experimental data and for the functionality of chaperones, as local dynamics facilitate rapid client release, folding on and from the chaperone surface, and client recognition without shape complementarity. Facilitated by the local dynamics, at least some chaperones appear to specifically recognize energetically frustrated sites of partially folded client proteins, such that the release of frustration contributes to the interaction affinity.
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?
Reshaping of dynamic client interactions upon Hsp90 conformational changes is critical for promoting structural transitions of the bound clients.
“Reshaping of dynamic client interactions upon Hsp90 conformational changes is critical for promoting structural transitions of the bound clients (71, 72).”
From Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network (2021) · cites this paper as [72]
Cites
NMR with Proteins and Nucleic Acids
Wüthrich, K. (1986) · Europhysics news · doi:10.1051/epn/19861701011 · Cited by 8,025 · see citing works
NMR of Proteins and Nucleic Acids
(2006) · Royal Society of Chemistry eBooks · doi:10.1039/9781847555236-00336 · Cited by 5,863 · see citing works
Molecular chaperones in protein folding and proteostasis
Hartl, F. U., Bracher, A., & Hayer-Hartl, M. K. (2011) · Nature · doi:10.1038/nature10317 · Cited by 3,525 · see citing works
Molecular Chaperones and Protein Quality Control
Bukau, B., Weissman, J. S., & Horwich, A. L. (2006) · Cell · doi:10.1016/j.cell.2006.04.014 · Cited by 1,556 · see citing works
Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
The crystal structure of the bacterial chaperonln GroEL at 2.8 Å
Braig, K., Otwinowski, Z., Hegde, R. S., Boisvert, D. C., Joachimiak, A., Horwich, A. L., & Sigler, P. B. (1994) · Nature · doi:10.1038/371578a0 · Cited by 1,321 · see citing works
Onuchic, J. N., & Wolynes, P. G. (2004) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2004.01.009 · Cited by 1,298 · see citing works
X-ray structure of a protein-conducting channel
van den Berg, B., Clemons, W., Collinson, I. R., Modis, Y., Hartmann, E., Harrison, S. C., & Rapoport, T. A. (2003) · Nature · doi:10.1038/nature02218 · Cited by 1,236 · see citing works
Structure of TPR Domain–Peptide Complexes
Scheufler, C., Brinker, A., Bourenkov, G., Pegoraro, S., Moroder, L., Bartunik, H., Hartl, F. U., & Moarefi, I. (2000) · Cell · doi:10.1016/s0092-8674(00)80830-2 · Cited by 1,188 · see citing works
Crystal structure of an Hsp90–nucleotide–p23/Sba1 closed chaperone complex
Ali, M. M. U., Roe, S. M., Vaughan, C. K., Meyer, P., Panaretou, B., Piper, P. W., Prodromou, C., & Pearl, L. H. (2006) · Nature · doi:10.1038/nature04716 · Cited by 962 · cited 1× · see citing works
“Crystal structures of the apo (client-free) forms of many molecular chaperones have long been available (15-23), but high-resolution structural descriptions of chaperones in complex with their clients have only recently become available.”
BackgroundPathways of cellular proteostasis in aging and disease
Klaips, C. L., Jayaraj, G. G., & Hartl, F. U. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201709072 · Cited by 803 · see citing works
Hartl, F. U. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044518 · Cited by 519 · see citing works
Structural insight into the biogenesis of β-barrel membrane proteins
Noinaj, N., Kuszak, A. J., Gumbart, J. C., et al. (2013) · Nature · doi:10.1038/nature12521 · Cited by 446 · see citing works
Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase
Verba, K. A., Wang, R. Y.-R., Arakawa, A., Liu, Y., Shirouzu, M., Yokoyama, S., & Agard, D. A. (2016) · Science · doi:10.1126/science.aaf5023 · Cited by 424 · see citing works
Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins
Ferbitz, L., Maier, T., Patzelt, H., Bukau, B., Deuerling, E., & Ban, N. (2004) · Nature · doi:10.1038/nature02899 · Cited by 419 · see citing works
Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones.
Kityk, R., Kopp, J., Sinning, I., & Mayer, M. P. (2012) · Molecules and Cells · doi:10.1016/j.molcel.2012.09.023 · Cited by 412 · see citing works
Kirschke, E., Goswami, D., Southworth, D., Griffin, P. R., & Agard, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.04.038 · Cited by 399 · see citing works
Hsp90-Tau complex reveals molecular basis for specificity in chaperone action
Karagöz, G. E., Duarte, A. M. S., Akoury, E., Ippel, H., Biernat, J., Morán Luengo, T., Radli, M., Didenko, T., Nordhues, B. A., Veprintsev, D. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.037 · Cited by 318 · cited 2× · see citing works
“Just as for the Skp–Omp complex, this model underscores the importance of multiple non-specific low-affinity contacts to build up towards a global high affinity interaction by avidity (28).”
BackgroundFerreiro, D. U., Komives, E. A., & Wolynes, P. G. (2014) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583514000092 · Cited by 314 · see citing works
Structural basis of outer membrane protein insertion by the BAM complex
Gu, Y., Li, H. Z., Dong, H., Zeng, Y. C., Zhang, Z., Paterson, N. G., Stansfeld, P. J., Wang, Z., Zhang, Y., Wang, W., et al. (2016) · Nature · doi:10.1038/nature17199 · Cited by 309 · see citing works
Gillespie, J. R., & Shortle, D. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.0954 · Cited by 297 · see citing works
Structural basis for protein antiaggregation activity of the trigger factor chaperone.
Saio, T., Guan, X., Rossi, P., Economou, A., & Kalodimos, C. G. (2014) · Science · doi:10.1126/science.1250494 · Cited by 289 · see citing works
Gillespie, J. R., & Shortle, D. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.0953 · Cited by 273 · see citing works
Mechanisms and Functions of Spatial Protein Quality Control
Sontag, E. M., Samant, R. S., & Frydman, J. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014616 · Cited by 269 · see citing works
Parra, R. G., Schafer, N. P., Radusky, L., Tsai, M., Guzovsky, A. B., Wolynes, P. G., & Ferreiro, D. U. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw304 · Cited by 263 · see citing works
Unraveling the Mechanism of Protein Disaggregation Through a ClpB-DnaK Interaction
Rosenzweig, R., Moradi, S., Zarrine‐Afsar, A., Glover, J. R., & Kay, L. E. (2013) · Science · doi:10.1126/science.1233066 · Cited by 259 · see citing works
Genetic Evidence for Parallel Pathways of Chaperone Activity in the Periplasm of Escherichia coli
Rizzitello, A. E., HARPER, J. R., & Silhavy, T. J. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.23.6794-6800.2001 · Cited by 254 · see citing works
Zhuravleva, A., Clerico, E. M., & Gierasch, L. (2012) · Cell · doi:10.1016/j.cell.2012.11.002 · Cited by 253 · see citing works
Structural basis of Sec-independent membrane protein insertion by YidC
Kumazaki, K., Chiba, S., Takemoto, M., Furukawa, A., Nishiyama, K., Sugano, Y., Mori, T., Dohmae, N., Hirata, K., Nakada-Nakura, Y., et al. (2014) · Nature · doi:10.1038/nature13167 · Cited by 247 · see citing works
The Crystal Structure of a GroEL/Peptide Complex
Chen, L., & Sigler, P. B. (1999) · Cell · doi:10.1016/s0092-8674(00)81673-6 · Cited by 242 · see citing works
Crystal Structure of the Mitochondrial Chaperone TIM9•10 Reveals a Six-Bladed α-Propeller
Webb, C. T., Gorman, M. A., Lazarou, M., Ryan, M. T., & Gulbis, J. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2005.11.010 · Cited by 229 · see citing works
Walton, T. A., & Sousa, M. C. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.07.023 · Cited by 222 · see citing works
Bitto, E., & McKay, D. B. (2002) · Structure · doi:10.1016/s0969-2126(02)00877-8 · Cited by 196 · see citing works
Mechanics of Hsp70 chaperones enables differential interaction with client proteins
Schlecht, R., Erbse, A. H., Bukau, B., & Mayer, M. P. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2006 · Cited by 194 · see citing works
Prospects for lanthanides in structural biology by NMR
Otting, G. (2008) · Journal of Biomolecular NMR · doi:10.1007/s10858-008-9256-0 · Cited by 183 · see citing works
Structural basis for the antifolding activity of a molecular chaperone
Huang, C., Rossi, P., Saio, T., & Kalodimos, C. G. (2016) · Nature · doi:10.1038/nature18965 · Cited by 168 · see citing works
Promiscuous Substrate Recognition in Folding and Assembly Activities of the Trigger Factor Chaperone
Martı́nez-Hackert, E., & Hendrickson, W. A. (2009) · Cell · doi:10.1016/j.cell.2009.07.044 · Cited by 167 · see citing works
Lavery, L. A., Partridge, J. R., Ramelot, T. A., Elnatan, D., Kennedy, M. A., & Agard, D. A. (2014) · Molecular Cell · doi:10.1016/j.molcel.2013.12.023 · Cited by 158 · see citing works
Horwich, A. L., & Fenton, W. A. (2009) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583509004764 · Cited by 154 · see citing works
The Structural Basis of Substrate Recognition by the Eukaryotic Chaperonin TRiC/CCT
Joachimiak, Ł. A., Walzthoeni, T., Liu, C. W., Aebersold, R. H., & Frydman, J. (2014) · Cell · doi:10.1016/j.cell.2014.10.042 · Cited by 149 · see citing works
Korndörfer, I. P., Dommel, M. K., & Skerra, A. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb828 · Cited by 143 · see citing works
Mapping Long-range Contacts in a Highly Unfolded Protein
Lietzow, M. A., Jamin, M., Dyson, H. J., & Wright, P. E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00847-1 · Cited by 143 · see citing works
The structural basis of autotransporter translocation by TamA
Gruss, F., Zähringer, F., Jakob, R. P., et al. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2689 · Cited by 138 · see citing works
Multidomain structure and correlated dynamics determined by self-consistent FRET networks
Hellenkamp, B., Wortmann, P., Kandzia, F., Zacharias, M., & Hugel, T. (2017) · Nature Methods · doi:10.1038/nmeth.4081 · Cited by 137 · see citing works
GroEL/ES Chaperonin Modulates the Mechanism and Accelerates the Rate of TIM-Barrel Domain Folding
Georgescauld, F., Popova, K. M., Gupta, A. J., et al. (2014) · Cell · doi:10.1016/j.cell.2014.03.038 · Cited by 135 · see citing works
Burmann, B. M., Wang, C., & Hiller, S. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2677 · Cited by 132 · see citing works
Self-citationThe client protein p53 adopts a molten globule–like state in the presence of Hsp90
Park, S. J., Borin, B. N., Martinez-Yamout, M. A., & Dyson, H. J. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2045 · Cited by 128 · see citing works
Frustration, function and folding
Ferreiro, D. U., Komives, E. A., & Wolynes, P. G. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.09.006 · Cited by 127 · see citing works
Crystal structure of the bacterial protein export chaperone secB.
Xu, Z., Knafels, J. D., & Yoshino‐Koh, K. (2000) · Nature Structural Biology · doi:10.1038/82040 · Cited by 120 · see citing works
Impact of holdase chaperones Skp and SurA on the folding of β-barrel outer-membrane proteins
Thoma, J., Burmann, B. M., Hiller, S., & Müller, D. J. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3087 · Cited by 113 · see citing works
Self-citationJahn, M., Rehn, A., Pelz, B., Hellenkamp, B., Richter, K., Rief, M., Büchner, J., & Hugel, T. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414073111 · Cited by 110 · see citing works
Targeting disordered proteins with small molecules using entropy
Heller, G. T., Sormanni, P., & Vendruscolo, M. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.07.004 · Cited by 104 · see citing works
Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins
Goloubinoff, P., Sassi, A. S., Fauvet, B., Barducci, A., & Rios, P. D. L. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0013-8 · Cited by 104 · see citing works
Xu, X., Wang, S., Hu, Y., et al. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.07.069 · Cited by 98 · see citing works
How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches
Verba, K. A., & Agard, D. A. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.07.002 · Cited by 98 · see citing works
Libich, D. S., Tugarinov, V., & Clore, G. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510083112 · Cited by 96 · see citing works
Mapping the conformation of a client protein through the Hsp70 functional cycle
Sekhar, A., Rosenzweig, R., Bouvignies, G., & Kay, L. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508504112 · Cited by 95 · see citing works
Subunit conformational variation within individual GroEL oligomers resolved by Cryo-EM
Roh, S., Hryc, C., Jeong, H.-H., Fei, X., Jakana, J., Lorimer, G., & Chiu, W. (2017) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1704725114 · Cited by 94 · see citing works
Skp is a multivalent chaperone of outer-membrane proteins
Schiffrin, B., Calabrese, A. N., Devine, P. W. A., Harris, S. A., Ashcroft, A. E., Brockwell, D. J., & Radford, S. E. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3266 · Cited by 92 · see citing works
Substrate protein folds while it is bound to the ATP-independent chaperone Spy
Stull, F. W., Koldewey, P., Humes, J. R., et al. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3133 · Cited by 86 · see citing works
Probing the transient dark state of substrate binding to GroEL by relaxation-based solution NMR
Libich, D. S., Fawzi, N. L., Ying, J., & Clore, G. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305715110 · Cited by 84 · see citing works
Tsuboyama, K., Tadakuma, H., & Tomari, Y. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.04.010 · Cited by 83 · see citing works
A molecular mechanism of chaperone-client recognition
He, L., Sharpe, T., Mazur, A., & Hiller, S. (2016) · Science Advances · doi:10.1126/sciadv.1601625 · Cited by 78 · see citing works
Self-citationYang, J., Zong, Y., Su, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01310-z · Cited by 78 · see citing works
Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery
Ratzke, C., Hellenkamp, B., & Hugel, T. (2014) · Nature Communications · doi:10.1038/ncomms5192 · Cited by 73 · see citing works
Kopp, M. C., Nowak, P. R., Larburu, N., Adams, C. J., & Ali, M. M. U. (2018) · eLife · doi:10.7554/elife.30257 · Cited by 73 · see citing works
Allosteric Regulation Points Control the Conformational Dynamics of the Molecular Chaperone Hsp90
Rehn, A., Moroni, E., Zierer, B. K., Tippel, F., Morra, G., John, C., Richter, K., Colombo, G., & Büchner, J. (2016) · Journal of Molecular Biology · doi:10.1016/j.jmb.2016.09.014 · Cited by 64 · see citing works
The dynamic dimer structure of the chaperone Trigger Factor
Morgado, L., Burmann, B. M., Sharpe, T., Mazur, A., & Hiller, S. (2017) · Nature Communications · doi:10.1038/s41467-017-02196-7 · Cited by 59 · see citing works
Self-citationMechanistic basis for the recognition of a misfolded protein by the molecular chaperone Hsp90
Oroz, J., Kim, J. H., Chang, B. J., & Zweckstetter, M. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3380 · Cited by 58 · see citing works
Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate
Rosam, M., Krader, D., Nickels, C., Hochmair, J., Back, K. C., Agam, G. N., Barth, A., Zeymer, C., Hendrix, J., Schneider, M., et al. (2017) · Nature Structural & Molecular Biology · doi:10.1038/s41594-017-0012-6 · Cited by 50 · see citing works
Folding while bound to chaperones
Horowitz, S. A., Koldewey, P., Stull, F. W., & Bardwell, J. C. A. (2017) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2017.06.009 · Cited by 48 · see citing works
Rios, P. D. L., & Goloubinoff, P. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3283 · Cited by 44 · see citing works
Protein Folding Mediated by Trigger Factor and Hsp70: New Insights from Single-Molecule Approaches
Wruck, F., Avellaneda, M. J., Koers, E. J., Minde, D., Mayer, M. P., Krämer, G., Mashaghi, A., & Tans, S. J. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.09.004 · Cited by 41 · see citing works
Chaperones and chaperone–substrate complexes: Dynamic playgrounds for NMR spectroscopists
Burmann, B. M., & Hiller, S. (2015) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2015.02.004 · Cited by 40 · see citing works
Self-citationStructural Mapping of a Chaperone–Substrate Interaction Surface
Callon, M., Burmann, B. M., & Hiller, S. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201310963 · Cited by 33 · see citing works
Self-citationAssaying the kinetics of protein denaturation catalyzed by AAA+ unfolding machines and proteases
Baytshtok, V., Baker, T. A., & Sauer, R. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505881112 · Cited by 32 · see citing works
Capturing a Dynamic Chaperone–Substrate Interaction Using NMR-Informed Molecular Modeling
Salmon, L., Ahlstrom, L. S., Horowitz, S. A., Dickson, A., Brooks, C. L., & Bardwell, J. C. A. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b02382 · Cited by 30 · see citing works
The chaperone toolbox at the single‐molecule level: From clamping to confining
Avellaneda, M. J., Koers, E. J., Naqvi, M. M., & Tans, S. J. (2017) · Protein Science · doi:10.1002/pro.3161 · Cited by 29 · see citing works
Libich, D. S., Tugarinov, V., Ghirlando, R., et al. (2017) · Biochemistry · doi:10.1021/acs.biochem.6b01237 · Cited by 28 · see citing works
Common Patterns in Chaperone Interactions with a Native Client Protein
He, L., & Hiller, S. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201713064 · Cited by 27 · see citing works
Self-citationNon-equilibrium conformational dynamics in the function of molecular chaperones
Barducci, A., & Rios, P. D. L. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.02.008 · Cited by 21 · see citing works
Chaperone–client complexes: A dynamic liaison
Hiller, S., & Burmann, B. M. (2018) · Journal of Magnetic Resonance · doi:10.1016/j.jmr.2017.12.008 · Cited by 21 · see citing works
Self-citationEarly stages in the biogenesis of eukaryotic β‐barrel proteins
Jores, T., & Rapaport, D. (2017) · FEBS Letters · doi:10.1002/1873-3468.12726 · Cited by 11 · see citing works
Hartl, F. U., & Hayer-Hartl, M. K. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3665 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Client binding shifts the populations of dynamic Hsp90 conformations through an allosteric network
Lopez, A., Dahiya, V., Delhommel, F., Freiburger, L., Stehle, R., Asami, S., Rutz, D., Blair, L., Buchner, J., & Sattler, M. (2021) · Science Advances · doi:10.1126/sciadv.abl7295 · Cited by 59 · see citing works
- Authors
- Hiller, S.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Hiller, Sebastian
- ORCID
- Hiller, Sebastian
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 44
- Issue
- 6
- Pages
- 517-527
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2906694226
- Cited by
- 54
- References
- 84
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 20 · 2021: 3 · 2020: 5 · 2019: 5
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- green
- edoc.unibas.ch
- Licence
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion, other-oa)
- Funders
- Swiss National Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- molecular chaperones, chaperone-client interactions, conformational ensembles, local dynamics, protein folding
- MeSH terms
- Humans, Protein Conformation, Thermodynamics, Protein Folding, Molecular Chaperones, Nuclear Magnetic Resonance, Biomolecular, Periplasmic Proteins
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