The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Structure of the FKBP12-Rapamycin Complex Interacting with Binding Domain of Human FRAP
Abstract
Rapamycin, a potent immunosuppressive agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP). A crystal structure of the ternary complex of human FKBP12, rapamycin, and the FKBP12-rapamycin-binding (FRB) domain of human FRAP at a resolution of 2.7 angstroms revealed the two proteins bound together as a result of the ability of rapamycin to occupy two different hydrophobic binding pockets simultaneously. The structure shows extensive interactions between rapamycin and both proteins, but fewer interactions between the proteins. The structure of the FRB domain of FRAP clarifies both rapamycin-independent and -dependent effects observed for mutants of FRAP and its homologs in the family of proteins related to the ataxia-telangiectasia mutant gene product, and it illustrates how a small cell-permeable molecule can mediate protein dimerization.
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.
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
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116
Self-citationChemistry and Biology of the Immunophilins and Their Immunosuppressive Ligands
Schreiber, S. L. (1991) · Science · doi:10.1126/science.1702904 · Cited by 1,494
Self-citation
Cited by
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Thoreen, C. C., Kang, S. A., Chang, J. W., Liu, Q., Zhang, J., Gao, Y., Reichling, L. J., Sim, T., Sabatini, D. M., & Gray, N. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900301200 · Cited by 1,803
Regulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093
mTOR kinase structure, mechanism and regulation
Yang, H., Rudge, D. G., Koos, J. D., Vaidialingam, B., Yang, H. J., & Pavletich, N. P. (2013) · Nature · doi:10.1038/nature12122 · Cited by 1,075
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055
Self-citationMechanisms of mTORC1 activation by RHEB and inhibition by PRAS40
Yang, H., Jiang, X., Li, B., Yang, H. J., Miller, M., Yang, A., Dhar, A., & Pavletich, N. P. (2017) · Nature · doi:10.1038/nature25023 · Cited by 548
Modulators of Protein–Protein Interactions
Milroy, L.-G., Grossmann, T. N., Hennig, S., Brunsveld, L., & Ottmann, C. (2014) · Chemical Reviews · doi:10.1021/cr400698c · Cited by 497
mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling
Rodrik-Outmezguine, V. S., Chandarlapaty, S., Pagano, N. C., Poulikakos, P. I., Scaltriti, M., Moskatel, E., Baselga, J., Guichard, S., & Rosen, N. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0085 · Cited by 442
An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
Inoue, T., Heo, W. D., Grimley, J. S., Wandless, T. J., & Meyer, T. (2005) · Nature Methods · doi:10.1038/nmeth763 · Cited by 424
Structure of the Human mTOR Complex I and Its Implications for Rapamycin Inhibition
Yip, C. K., Murata, K., Walz, T., Sabatini, D. M., & Kang, S. A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.017 · Cited by 372
Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery
Dong, G., Ding, Y., He, S., & Sheng, C. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00895 · Cited by 369
Architecture of human mTOR complex 1
Aylett, C. H. S., Sauer, E., Imseng, S., Boehringer, D., Hall, M. N., Ban, N., & Maier, T. (2016) · Science · doi:10.1126/science.aaa3870 · Cited by 344
Hughes, S. J., & Ciulli, A. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170041 · Cited by 240
Fang, Z., Grütter, C., & Rauh, D. (2013) · ACS Chemical Biology · doi:10.1021/cb300663j · Cited by 197
Targeting Protein-Protein Interaction by Small Molecules
Jin, L., Wang, W., & Fang, G. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-140028 · Cited by 195
Cruz, M. C., Goldstein, A. L., Blankenship, J., Del Poeta, M., Perfect, J. R., McCusker, J. H., Bennani, Y. L., Cardenas, M. E., & Heitman, J. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.11.3162-3170.2001 · Cited by 159
Vilella-Bach, M., Nuzzi, P., Fang, Y., & Chen, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.7.4266 · Cited by 154
Self-citationRefined structure of the FKBP12–rapamycin–FRB ternary complex at 2.2 Å resolution
Liang, J., Choi, J., & Clardy, J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998014747 · Cited by 148
Self-citationCarlson, E. S., Stead, J. D. H., Neal, C. R., Petryk, A., & Georgieff, M. K. (2007) · Hippocampus · doi:10.1002/hipo.20307 · Cited by 141
Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity
Schreiber, S. L. (2024) · Cell Chemical Biology · doi:10.1016/j.chembiol.2024.05.004 · Cited by 112
Self-citationAnders, C., Higuchi, Y., Koschinsky, K., Bartel, M., Schumacher, B., Thiel, P., Nitta, H., Preisig-Müller, R., Schlichthörl, G., Renigunta, V., et al. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.03.015 · Cited by 106
Bifunctional chemical probes inducing protein–protein interactions
Maniaci, C., & Ciulli, A. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.07.003 · Cited by 100
4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1
Yang, H., Wang, J., Liu, M., Chen, X., Huang, M., Tan, D., Dong, M.-Q., Wong, C. C. L., Wang, J., Xu, Y., et al. (2016) · Protein & Cell · doi:10.1007/s13238-016-0346-6 · Cited by 96
Mining the CRBN target space redefines rules for molecular glue-induced neosubstrate recognition
Petzold, G., Gainza, P., Annunziato, S., Lamberto, I., Trenh, P., McAllister, L. A., DeMarco, B., Schwander, L., Bunker, R. D., Zlotosch, M., et al. (2025) · Science · doi:10.1126/science.adt6736 · Cited by 117
Relieving Autophagy and 4EBP1 from Rapamycin Resistance
Nyfeler, B., Bergman, P., Triantafellow, E., Wilson, C. J., Zhu, Y., Radetich, B., Finan, P. M., Klionsky, D. J., & Murphy, L. O. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05430-11 · Cited by 94
mTOR-Dependent Cell Proliferation in the Brain
Ryskalin, L., Lazzeri, G., Flaibani, M., Biagioni, F., Gambardella, S., Frati, A., & Fornai, F. (2017) · BioMed Research International · doi:10.1155/2017/7082696 · Cited by 86
Modulating Protein–Protein Interactions with Small Molecules: The Importance of Binding Hotspots
Thangudu, R. R., Bryant, S. H., Panchenko, A. R., & Madej, T. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.12.026 · Cited by 71
Nakatsu, Y., Sakoda, H., Kushiyama, A., Zhang, J., Ono, H., Fujishiro, M., Kikuchi, T., Fukushima, T., Yoneda, M., Ohno, H., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.206904 · Cited by 69
Drug Inducible CRISPR/Cas Systems
Zhang, J., Chen, L., Zhang, J., & Wang, Y. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.07.015 · Cited by 69
Proximity and orientation underlie signaling by the non‐receptor tyrosine kinase ZAP70
Graef, I. A., Holsinger, L. J., Diver, S., Schreiber, S. L., & Crabtree, G. R. (1997) · The EMBO Journal · doi:10.1093/emboj/16.18.5618 · Cited by 67
Self-citationRaptor downregulation rescues neuronal phenotypes in mouse models of Tuberous Sclerosis Complex
Karalis, V., Caval-Holme, F., & Bateup, H. S. (2022) · Nature Communications · doi:10.1038/s41467-022-31961-6 · Cited by 40
Wu, X., Wang, L., Han, Y., Regan, N., Li, P.-K., Villalona, M. A., Hu, X., Briesewitz, R., & Pei, D. (2011) · ACS Combinatorial Science · doi:10.1021/co200057n · Cited by 36
Distinct Repression of Translation by Wortmannin and Rapamycin
Pedersen, S., Celis, J. E., Nielsen, J., Christiansen, J., & Nielsen, F. C. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00449.x · Cited by 36
Brath, U., & Akke, M. (2009) · Journal of Molecular Biology · doi:10.1016/j.jmb.2009.01.047 · Cited by 36
Multi-timescale dynamics study of FKBP12 along the rapamycin–mTOR binding coordinate
Sapienza, P. J., Mauldin, R. V., & Lee, A. L. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.10.037 · Cited by 32
Salgania, H. K., Metz, J., & Jeske, M. (2024) · Nature Communications · doi:10.1038/s41467-024-47233-4 · Cited by 17
Discovery of molecular glues that bind FKBP12 and novel targets using DNA-barcoded libraries
Zandi, T. A., Romanowski, M. J., Viscomi, J. S., Tan, Z. Y., Tong, B., Bonazzi, S., Zécri, F. J., Schreiber, S. L., & Michaud, G. A. (2024) · doi:10.1101/2024.12.09.627499 · Cited by 10
Self-citationAdhikari, B., Schneider, K., Diebold, M., Sotriffer, C., & Wolf, E. (2024) · eLife · doi:10.7554/elife.98450 · Cited by 4
Metadata
- Authors
- Choi, J., Chen, J., Schreiber, S. L., & Clardy, J.
- Venue
- Science
- Published
- 1996-07-12
- Volume
- 273
- Issue
- 5272
- Pages
- 239-242
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2007110714
- Cited by
- 929
- References
- 2
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- closed
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
