The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Cryo-electron microscopy reveals a single domain antibody with a unique binding epitope on fibroblast activation protein alpha
Open accessPreprint — published as 10.1039/d4cb00267a · Paper page
Abstract
Fibroblast activation protein alpha (FAP) is a serine protease that is expressed at basal levels in benign tissues but is overexpressed in a variety of pathologies, including cancer. Despite this unique expression profile, designing effective diagnostic and therapeutic agents that effectively target this biomarker remain elusive. Here we report the structural characterization of the interaction between a novel single domain antibody (sdAbs), I3, and FAP using cryo-electron microscopy. The reconstructions were determined to a resolution of 2.7 Å and contained two distinct populations; one I3 bound and two I3 molecules bound to the FAP dimer. In both cases, the sdAbs bound a unique epitope that was distinct from the active site of the enzyme. Furthermore, this report describes the rational mutation of specific residues within the complementarity determining region 3 (CDR3) loop to enhance affinity and selectivity of the I3 molecule for FAP. This report represents the first sdAb-FAP structure to be described in the literature.
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
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 49
- 10.3233/HAB-200425 · DOI
- 2021, Nanobodies: The Future of Antibody-Based Immune Therapeutics, Cancer Biother Radiopharm, 36, 109
- 10.1002/anie.201708459 · DOI
- 10.1016/j.drudis.2022.03.013 · DOI
- 10.3389/fonc.2020.01182 · DOI
- 10.3389/fimmu.2015.00387 · DOI
- 10.1111/j.1742-4658.2009.07526.x · DOI
- 10.2174/156652412803833607 · DOI
- 10.1517/14728220903103841 · DOI
- 10.1038/s41388-018-0275-3 · DOI
- 10.1002/prca.201300095 · DOI
- 10.1148/radiol.220749 · DOI
- Sidrak, M. M. A. ; De Feo, M. S. ; Corica, F. ; Gorica, J. ; Conte, M. ; Filippi, L. ; Schillaci, O. ; De Vincentis, G. ; Frantellizzi, V . Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics-Where We Are at and Where We Are Heading: A Systematic Review. Int J Mol Sci 2023, 24. · DOI
- Gilardi, L. ; Airo Farulla, L. S. ; Demirci, E. ; Clerici, I. ; Omodeo Sale, E. ; Ceci, F . Imaging Cancer-Associated Fibroblasts (CAFs) with FAPi PET. Biomedicines 2022, 10. · DOI
- Lindner, T. ; Giesel, F. L. ; Kratochwil, C. ; Serfling, S. E . Radioligands Targeting Fibroblast Activation Protein (FAP). Cancers (Basel) 2021, 13. · DOI
- 10.1186/s13550-021-00761-2 · DOI
- Windisch, P. ; Zwahlen, D. R. ; Koerber, S. A. ; Giesel, F. L. ; Debus, J. ; Haberkorn, U. ; Adeberg, S . Clinical Results of Fibroblast Activation Protein (FAP) Specific PET and Implications for Radiotherapy Planning: Systematic Review. Cancers (Basel) 2020, 12. · DOI
- Pandya, D. N. ; Sinha, A. ; Yuan, H. ; Mutkus, L. ; Stumpf, K. ; Marini, F. C. ; Wadas, T. J . Imaging of Fibroblast Activation Protein Alpha Expression in a Preclinical Mouse Model of Glioma Using Positron Emission Tomography. Molecules 2020, 25. · DOI
- Xu, J. ; Li, S. ; Xu, S. ; Dai, J. ; Luo, Z. ; Cui, J. ; Cai, F. ; Geng, C. ; Wang, Z. ; Tang, X . Screening and Preclinical Evaluation of Novel Radiolabeled Anti-Fibroblast Activation Protein-alpha Recombinant Antibodies. Cancer Biother Radiopharm 2022. · DOI
- 10.1021/cr900325h · DOI
- 10.1007/s00259-022-05757-1 · DOI
- 10.2967/jnumed.123.266381 · DOI
- Tafreshi, N. K. ; Doligalski, M. L. ; Tichacek, C. J. ; Pandya, D. N. ; Budzevich, M. M. ; El-Haddad, G. ; Khushalani, N. I. ; Moros, E. G. ; McLaughlin, M. L. ; Wadas, T. J. ; Morse, D. L . Development of Targeted Alpha Particle Therapy for Solid Tumors. Molecules 2019, 24. · DOI · Paper page
- 10.1042/ETLS20200295 · DOI
- 10.1016/j.bbrc.2022.08.078 · DOI
- 10.1021/acs.biochem.5b00114 · DOI
- 10.1042/EBC20170032 · DOI
- 10.1016/j.sbi.2018.10.006 · DOI
- 10.18388/pb.2016_43 · DOI
- 10.1016/j.tibs.2019.04.008 · DOI
- 2018, Biological Applications at the Cutting Edge of Cryo-Electron Microscopy, Microsc Microanal, 24, 406, 10.1017/S1431927618012382 · DOI
- 10.1016/j.sbi.2022.102484 · DOI
- 10.1038/nrd.2018.77 · DOI
- 10.1074/jbc.C500092200 · DOI
- Epitope Mapping Protocols; 3 ed.; Humanna Press, 2018.
- 10.1016/j.drudis.2014.05.011 · DOI
- 10.1080/02648725.2007.10648092 · DOI
- 10.1038/srep31365 · DOI
- 10.1016/j.intimp.2022.109237 · DOI
- 10.1080/14728222.2017.1370455 · DOI
- 10.1093/eurheartj/ehq519 · DOI
- 10.1007/s10555-020-09909-3 · DOI
- 10.1186/1475-2859-10-44 · DOI
- Nathaniel R. Bennett , V. L. W., Robert J. Ragotte , Andrew J. Borst , Déjenaé L. See , Connor Weidle , Riti Biswas , Ellen L. Shrock , Philip J. Y. Leung , Buwei Huang , Inna Goreshnik , Russell Ault , Kenneth D. Carr , Benedikt Singer , Cameron Criswell , Dionne Vafeados , Mariana Garcia Sanchez , Ho Min Kim , Susana Vázquez Torres , Sidney Chan , David Baker Atomically accurate de novo design of single-domain antibodies. bioRxiv 2024, 1–30. · DOI · Paper page
- 10.1038/nmeth.4169 · DOI · Paper page
- 10.1002/jcc.20084 · DOI
- 10.1107/S0907444910007493 · DOI · Paper page
- 10.1107/S2059798319011471/HTTPS://GOLDBOOK.IUPAC.ORG/E02002.HTML · DOI
- 10.7554/eLife.01456 · DOI
Metadata
- Authors
- Xu, Z., Sinha, A., Pandya, D. N., Schnicker, N. J., & Wadas, T. J.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Schnicker, Nicholas J.
- Wadas, Thaddeus J.
- Venue
- RSC Chemical Biology
- Publisher
- openRxiv
- Published
- 2024-10-20
- Volume
- 6
- Issue
- 5
- Pages
- 780-787
- ISSN
- 2633-0679 (ISSN-L)
- PMC
- PMC11834968
- OpenAlex
- W4407219915
- Cited by
- 5
- References
- 1
- Citations by year
- 2026: 3 · 2025: 2
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- RSC Chemical Biology (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc)
- Funders
- University of Pennsylvania
- Division of Cancer Prevention, National Cancer Institute (P30 CA086862, R21-CA219899, R21-CA227709)
- Iowa State University
- Perelman School of Medicine, University of Pennsylvania
- Holden Comprehensive Cancer Center, University of Iowa (P30-CA086862)
- Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- National Cancer Institute (R21CA219899, R21CA227709, P30CA086862)
- Congressionally Directed Medical Research Programs (W81XWH-19-1-0046)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- fibroblast activation protein, nanobodies, antibody-antigen complex structure, binding epitope, serine protease, CDR3, protein dimer
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
