Cited by 169Monoclonal and Polyclonal Antibodies ResearchProtein Structure and DynamicsEnzyme Structure and Function

The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index.

Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies

Zavrtanik, Uroš, Lukan, Junoš, Loris, Remy, Lah, Jurij, Hadži, San·2018·Journal of Molecular Biology

DOI 10.1016/j.jmb.2018.09.002

Open this paper in CoChat — free account

Abstract

Truncated versions of heavy-chain antibodies (HCAbs) from camelids, also termed nanobodies, comprise only one-tenth the mass of conventional antibodies, yet retain similar, high binding affinities for the antigens. Here we analyze a large data set of nanobody-antigen crystal structures and investigate how nanobody-antigen recognition compares to the one by conventional antibodies. We find that nanobody paratopes are enriched in aromatic residues just like conventional antibodies, but additionally, they also bear a more hydrophobic character. Most striking differences were observed in the characteristics of the antigen's epitope. Unlike conventional antibodies, nanobodies bind to more rigid, concave, conserved and structured epitopes enriched with aromatic residues. Nanobodies establish fewer interactions with the antigens compared to conventional antibodies, and we speculate that high binding affinities are achieved due to less unfavorable conformational and more favorable solvation entropy contributions. We observed that interactions with antigen are mediated not only by three CDR loops but also by numerous residues from the nanobody framework. These residues are not distributed uniformly; rather, they are concentrated into four structurally distinct regions and mediate mostly charged interactions. Our findings suggest that in some respects nanobody-antigen interactions are more similar to the general protein-protein interactions rather than antibody-antigen interactions.

Integrity signals

Registry

Crossref · 10.1016/j.jmb.2018.09.002

Cites

87 of 87 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Silhouettes: A graphical aid to the interpretation and validation of cluster analysis
Rousseeuw, P. J. (1987) · Journal of Computational and Applied Mathematics · doi:10.1016/0377-0427(87)90125-7 · Cited by 21,392
Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320
Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences
Li, W.-Z., & Godzik, A. (2006) · Bioinform. · doi:10.1093/bioinformatics/btl158 · Cited by 10,996
Biopython: freely available python tools for computational molecular biology and bioinformatics
Cock, P. J. A., Antao, T., Chang, J. T., Chapman, B. A., Cox, C. J., Dalke, A., Friedberg, I., Hamelryck, T., Kauff, F., Wilczynski, B., et al. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp163 · Cited by 6,080
Biometry: The Principles and Practice of Statistics in Biological Research
Campbell, R. C., Sokal, R. R., & Rohlf, F. J. (1970) · Journal of the Royal Statistical Society Series A (General) · doi:10.2307/2343822 · Cited by 3,972
Prediction of protein antigenic determinants from amino acid sequences.
Hopp, T. P., & Woods, K. R. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.6.3824 · Cited by 3,726
Naturally occurring antibodies devoid of light chains
Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G., Hammers, C., Songa, E. B., Bendahman, N., & Hammers, R. (1993) · Nature · doi:10.1038/363446a0 · Cited by 3,241
ConSurf 2016: An improved methodology to estimate and visualize evolutionary conservation in macromolecules
Ashkenazy, H., Abadi, S., Martz, E., Chay, O., Mayrose, I., Pupko, T., & Ben-Tal, N. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw408 · Cited by 3,163
Nanobodies: natural single-domain antibodies
Muyldermans, S. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-063011-092449 · Cited by 2,304
Structure and function of immunoglobulins
Schroeder, H. W., & Cavacini, L. A. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.09.046 · Cited by 2,143

Flagged first, then by citations

Show all 87 references

Sorted by citations

The therapeutic potential of nanobodies
Jovčevska, I., & Muyldermans, S. (2020) · BioDrugs · doi:10.1007/s40259-019-00392-z · Cited by 749
NANOBODIES®: A Review of Diagnostic and Therapeutic Applications
Jin, B.-K., Odongo, S., Radwanska, M., & Magez, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065994 · Cited by 411
A guide to: generation and design of nanobodies
Muyldermans, S. (2020) · FEBS Journal · doi:10.1111/febs.15515 · Cited by 369
Applications of Nanobodies
Muyldermans, S. (2020) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-021419-083831 · Cited by 350
Immunogenicity and humanization of single‐domain antibodies
Rossotti, M. A., Bélanger, K., Henry, K. A., & Tanha, J. (2021) · FEBS Journal · doi:10.1111/febs.15809 · Cited by 180
Theranostics in immuno-oncology using nanobody derivatives
Lecocq, Q., Vlaeminck, Y. D., Hanssens, H., D’Huyvetter, M., Raes, G., Goyvaerts, C., Keyaerts, M., Devoogdt, N., & Breckpot, K. (2019) · Theranostics · doi:10.7150/thno.34941 · Cited by 146
Evolution of Escherichia coli Expression System in Producing Antibody Recombinant Fragments
Sandomenico, A., Sivaccumar, J. P., & Ruvo, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176324 · Cited by 134
“The extended CDR3 loop of nanobodies has the capacity to form a finger-like structure with greater structural flexibility which, in turn, is likely fixed in one single conformation upon antigen-binding [14,15].”
Background
Rapid generation of potent antibodies by autonomous hypermutation in yeast
Wellner, A., McMahon, C. T., Gilman, M. S. A., Clements, J. R., Clark, S. A., Nguyen, K. M., Ho, M. H., Hu, V. J., Shin, J.-E., Feldman, J. E., et al. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00832-4 · Cited by 133
An overview on display systems (phage, bacterial, and yeast display) for production of anticancer antibodies; advantages and disadvantages
Mahdavi, S. Z. B., Oroojalian, F., Eyvazi, S., Hejazi, M., Baradaran, B., Pouladi, N., Tohidkia, M. R., Mokhtarzadeh, A., & Muyldermans, S. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.03.113 · Cited by 115
Camelid Single-Domain Antibodies: Promises and Challenges as Lifesaving Treatments
Arbabi‐Ghahroudi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23095009 · Cited by 100
Exploring cellular biochemistry with nanobodies
Cheloha, R. W., Harmand, T. J., Wijne, C., Schwartz, T., & Ploegh, H. L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.012960 · Cited by 98
Fluonanobody-based nanosensor via fluorescence resonance energy transfer for ultrasensitive detection of ochratoxin A
Su, B., Zhang, Z., Sun, Z., Tang, Z., Xie, X., Chen, Q., Cao, H., Yu, X., Xu, Y., Liu, X., et al. (2021) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.126838 · Cited by 89
Nanobody-Targeted Photodynamic Therapy Selectively Kills Viral GPCR-Expressing Glioblastoma Cells
Groof, T. W. M. D., Mashayekhi, V., Fan, T. S., Bergkamp, N. D., Toraño, J. S., van Senten, J. R., Heukers, R., Smit, M. J., & Oliveira, S. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b00360 · Cited by 85
Nanobodies: Robust miniprotein binders in biomedicine
Kim, J. Y. J., Sang, Z., Xiang, Y., Shen, Z., & Shi, Y. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.114726 · Cited by 82
Application of Single-Domain Antibodies (“Nanobodies”) to Laboratory Diagnosis
Pillay, T. S., & Muyldermans, S. (2021) · Annals of Laboratory Medicine · doi:10.3343/alm.2021.41.6.549 · Cited by 77
Single-domain near-infrared protein provides a scaffold for antigen-dependent fluorescent nanobodies
Oliinyk, O. S., Baloban, M., Clark, C. L., Carey, E. M., Pletnev, S. V., Nimmerjahn, A., & Verkhusha, V. V. (2022) · Nature Methods · doi:10.1038/s41592-022-01467-6 · Cited by 73
Research progress and applications of nanobody in human infectious diseases
Mei, Y., Chen, Y., Sivaccumar, J. P., An, Z., Xia, N., & Luo, W. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.963978 · Cited by 73
Nanobody Conjugates for Targeted Cancer Therapy and Imaging
Kang, W., Ding, C., Zheng, D., Ma, X., Yi, L., Tong, X., Wu, C., Xue, C., Yu, Y., & Zhou, Q. (2021) · Technology in Cancer Research & Treatment · doi:10.1177/15330338211010117 · Cited by 64
COMBINES-CID: An Efficient Method for De Novo Engineering of Highly Specific Chemically Induced Protein Dimerization Systems
Kang, S., Davidsen, K., Gomez-Castillo, L., Jiang, H., Fu, X., Li, Z., Liang, Y. T., Jahn, M., Moussa, M., DiMaio, F., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b03522 · Cited by 64
Computational design and modeling of nanobodies toward SARS‐CoV‐2 receptor binding domain
Yang, J., Zhang, Z., Yang, F., Zhang, H., Wu, H., Zhu, F., & Xue, W. (2021) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13847 · Cited by 56
Homology Modeling-Based in Silico Affinity Maturation Improves the Affinity of a Nanobody
Cheng, X. M., Wang, J., Kang, G., Hu, M., Yuan, B., Zhang, Y., & Huang, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174187 · Cited by 57
Nanobodies: The Future of Antibody-Based Immune Therapeutics
Bathula, N. V., Bommadevara, H., & Hayes, J. M. (2020) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2020.3941 · Cited by 58
Targeted drug delivery using nanobodies to deliver effective molecules to breast cancer cells: the most attractive application of nanobodies
Abdolvahab, M. H., Karimi, P., Mohajeri, N., Abedini, M., & Zare, H. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03259-8 · Cited by 52
Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody
Akiba, H., Tamura, H., Kiyoshi, M., Yanaka, S., Sugase, K., Caaveiro, J. M. M., & Tsumoto, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-50722-y · Cited by 48
Prospects for the computational humanization of antibodies and nanobodies
Gordon, G. L., Raybould, M. I. J., Wong, A., & Deane, C. M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1399438 · Cited by 48
Nanobody‑horseradish peroxidase and -EGFP fusions as reagents to detect porcine parvovirus in the immunoassays
Lu, Q., Li, X., Zhao, J., Zhu, J.-H., Luo, Y., Duan, H. Q., Ji, P., Wang, K., Liu, B., Wang, X., et al. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-019-0568-x · Cited by 47
Nanobodies: From High-Throughput Identification to Therapeutic Development
Fridy, P. C., Rout, M. P., & Ketaren, N. E. (2024) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2024.100865 · Cited by 43
Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective
Lucas, A. T., Moody, A., Schorzman, A. N., & Zamboni, W. C. (2021) · Antibodies · doi:10.3390/antib10030030 · Cited by 40
Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
Liu, J., Wu, L., Xie, A., Liu, W. L., Zhao, H., Wan, Y., & Mao, W. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03169-5 · Cited by 42
A comparison of the binding sites of antibodies and single-domain antibodies
Gordon, G. L., Capel, H., Guloglu, B., Richardson, E., Stafford, R., & Deane, C. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1231623 · Cited by 40
Current status and future expectations of nanobodies in oncology trials
Pauw, T. D., Mey, L. D., Debacker, J. M., Raes, G., Ginderachter, J. A. V., Groof, T. W. M. D., & Devoogdt, N. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2249814 · Cited by 38
Nanobody engineering: computational modelling and design for biomedical and therapeutic applications
Salamouni, N. S. E., Cater, J. H., Spenkelink, L. M., & Yu, H. B. (2024) · FEBS Open Bio · doi:10.1002/2211-5463.13850 · Cited by 37
Single-Domain Antibodies Efficiently Neutralize SARS-CoV-2 Variants of Concern
Favorskaya, I. A., Shcheblyakov, D. V., Esmagambetov, I. B., Dolzhikova, I. V., Alekseeva, I. A., Korobkova, A. I., Voronina, D. V., Ryabova, E. I., Derkaev, A. A., Витальевна, К. А., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.822159 · Cited by 36
Molecular basis for thermal stability and affinity in a VHH: Contribution of the framework region and its influence in the conformation of the CDR3
Kinoshita, S., Nakakido, M., Mori, C., Kuroda, D., Caaveiro, J. M. M., & Tsumoto, K. (2022) · Protein Science · doi:10.1002/pro.4450 · Cited by 37
Identification of conformation-selective nanobodies against the membrane protein insertase BamA by an integrated structural biology approach
Kaur, H., Hartmann, J.-B., Jakob, R. P., Zahn, M., Zimmermann, I., Maier, T., Seeger, M. A., & Hiller, S. (2019) · Journal of Biomolecular NMR · doi:10.1007/s10858-019-00250-8 · Cited by 34
Advancements in Nanobody Epitope Prediction: A Comparative Study of AlphaFold2Multimer vs AlphaFold3
Eshak, F., & Goupil-Lamy, A. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c01877 · Cited by 34
Single-domain antibodies as therapeutics for solid tumor treatment
Wang, M., Ying, T., & Wu, Y. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.03.016 · Cited by 33
Delicate balance among thermal stability, binding affinity, and conformational space explored by single-domain VHH antibodies
Ikeuchi, E., Kuroda, D., Nakakido, M., Murakami, A., & Tsumoto, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-98977-8 · Cited by 32
Nanobodies targeting immune checkpoint molecules for tumor immunotherapy and immunoimaging (Review)
Yü, S., Gui, X., Zhao, S., Tang, Y., Tang, H., Wang, K., Liu, H., Lan, K., Bi, X., & Duan, S. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4817 · Cited by 30
Downsizing antibodies: Towards complementarity-determining region (CDR)-based peptide mimetics
holsbeeck, K. V., Martins, J. C., & Ballet, S. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.105563 · Cited by 30
Small but mighty: the versatility of nanobodies in modern medicine
Blueggel, M., Gül, D., Stauber, R. H., & Knauer, S. K. (2025) · Nanoscale Horizons · doi:10.1039/d5nh00283d · Cited by 29
Nanobodies – Little helpers unravelling intracellular signaling
Wagner, T. R., & Rothbauer, U. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.005 · Cited by 29
Structural Classification of CDR-H3 in Single-Domain VHH Antibodies
Kuroda, D., & Tsumoto, K. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2609-2_2 · Cited by 27
Research progress on unique paratope structure, antigen binding modes, and systematic mutagenesis strategies of single-domain antibodies
Liu, C., Lin, H., Cao, L., Wang, K., & Sui, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1059771 · Cited by 26
Expanding and improving nanobody repertoires using a yeast display method: Targeting SARS-CoV-2
Cross, F. R., Fridy, P. C., Ketaren, N. E., Mast, F. D., Li, S., Olivier, J. P., Pecani, K., Chait, B. T., Aitchison, J. D., & Rout, M. P. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.102954 · Cited by 21
From discovery to the clinic: structural insights, engineering options, clinical, and ‘next wave’ applications of camelid-derived single-domain antibodies
Evers, A., Guarnera, E., Pekar, L., & Zielonka, S. (2025) · mAbs · doi:10.1080/19420862.2025.2583210 · Cited by 23
Identification, binding, and structural characterization of single domain anti-PD-L1 antibodies inhibitory of immune regulatory proteins PD-1 and CD80
Kang-Pettinger, T., Walker, K., Brown, R., Cowan, R. H., Wright, H., Baravalle, R., Waters, L. C., Muskett, F. W., Bowler, M. W., Sawmynaden, K., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102769 · Cited by 21
Identification of nanobodies against hepatocellular carcinoma marker glypican-3
Wang, W., Xu, C., Wang, H., & Jiang, C. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.01.010 · Cited by 20
Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines
Fernández‐Quintero, M. L., Pomarici, N. D., Fischer, A.-L. M., Hoerschinger, V. J., Kroell, K. B., Riccabona, J. R., Kamenik, A. S., Loeffler, J. R., Ferguson, J. A., Perrett, H. R., et al. (2023) · Antibodies · doi:10.3390/antib12040067 · Cited by 21
Unique mechanisms to increase structural stability and enhance antigen binding in nanobodies
Ketaren, N. E., Fridy, P. C., Malashkevich, V. N., Sanyal, T., Brillantes, M., Thompson, M. K., Oren, D. A., Bonanno, J. B., Šali, A., Almo, S. C., et al. (2025) · Structure · doi:10.1016/j.str.2025.01.019 · Cited by 19
Arabidopsis immunity regulator EDS1 in a PAD4/SAG101-unbound form is a monomer with an inherently inactive conformation
Voss, M., Toelzer, C., Bhandari, D. D., Parker, J. E., & Niefind, K. (2019) · Journal of Structural Biology · doi:10.1016/j.jsb.2019.09.007 · Cited by 19
A nanobody toolbox targeting dimeric coiled-coil modules for functionalization of designed protein origami structures
Majerle, A., Hadži, S., Aupič, J., Satler, T., Lapenta, F., Strmšek, Ž., Lah, J., Loris, R., & Jerala, R. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021899118 · Cited by 19
Self-citation
NbX: Machine Learning-Guided Re-Ranking of Nanobody–Antigen Binding Poses
Tam, C., Kumar, A., & Zhang, K. Y. J. (2021) · Pharmaceuticals · doi:10.3390/ph14100968 · Cited by 17
A non-redundant data set of nanobody-antigen crystal structures
Zavrtanik, U., & Hadži, S. (2019) · Data in Brief · doi:10.1016/j.dib.2019.103754 · Cited by 17
Self-citation
In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design
Yu, H., Mao, G., Pei, Z., Cen, J., Meng, W., Wang, Y., Zhang, S., Li, S., Xu, Q., Sun, M., et al. (2023) · Molecules · doi:10.3390/molecules28196838 · Cited by 16
Nanobody Paratope Ensembles in Solution Characterized by MD Simulations and NMR
Fernández‐Quintero, M. L., DeRose, E. F., Gabel, S. A., Mueller, G. A., & Liedl, K. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105419 · Cited by 16
Tuning Nanobodies’ Bioactivity: Coupling to Ultrasmall Gold Nanoparticles Allows the Intracellular Interference with Survivin
Stahl, P., Kollenda, S., Sager, J., Schmidt, L., Schroer, M. A., Stauber, R. H., Epple, M., & Knauer, S. K. (2023) · Small · doi:10.1002/smll.202300871 · Cited by 15
Single‐Domain Antibody‐Based TCR‐Like CAR‐T: A Potential Cancer Therapy
Zhu, L., Yang, X., Zhong, D., Xie, S., Shi, W., Li, Y., Hou, X., HuaYao, Zhou, H., Zhao, M., et al. (2020) · Journal of Immunology Research · doi:10.1155/2020/2454907 · Cited by 14
Nanobody-Based Drug Delivery: Emerging Strategies for Targeted Cancer Therapy
Ghosh, N., Sepay, N., Paul, M., & Im, J. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s584604 · Cited by 14
PLAbDab-nano: a database of camelid and shark nanobodies from patents and literature
Gordon, G. L., Greenshields‐Watson, A., Agarwal, P., Wong, A., Boyles, F., Hummer, A. M., Hernandez, A. G. L., & Deane, C. M. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae881 · Cited by 13
Isolation and structural characterization of a Zn2+-bound single-domain antibody against NorC, a putative multidrug efflux transporter in bacteria
Kumar, S., Mahendran, I., Athreya, A., Ranjan, R. D., & Penmatsa, A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010902 · Cited by 13
Computer-guided library generation applied to the optimization of single-domain antibodies
Akiba, H., Tamura, H., Caaveiro, J. M. M., & Tsumoto, K. (2019) · Protein Engineering Design and Selection · doi:10.1093/protein/gzaa006 · Cited by 13
A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria
Chen, P.-Y., Chen, Y.-C., Chen, P.-P., Lin, K.-T., Sargsyan, K., Hsu, C., Wang, W.-L., Hsia, K., & Ting, S. (2024) · Nature Communications · doi:10.1038/s41467-024-51017-1 · Cited by 12
Development of novel humanized VHH synthetic libraries based on physicochemical analyses
Nakakido, M., Kinoshita, S., & Tsumoto, K. (2024) · Scientific Reports · doi:10.1038/s41598-024-70513-4 · Cited by 12
Interaction standards for biophysics: anti-lysozyme nanobodies
Birchenough, H. L., Nivia, H. D. R., & Jowitt, T. A. (2021) · European Biophysics Journal · doi:10.1007/s00249-021-01524-6 · Cited by 12
Development of nanobodies against Staphylococcus enterotoxin B through yeast surface display
Ming, K., Hu, Y., Zhu, M. J., Xing, B., Mei, M., & Wei, Z. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.126822 · Cited by 12
Broad Reactivity Single Domain Antibodies against Influenza Virus and Their Applications to Vaccine Potency Testing and Immunotherapy
Yep, A. T., Takeuchi, Y., Engelhardt, O. G., & Hufton, S. E. (2021) · Biomolecules · doi:10.3390/biom11030407 · Cited by 12
Structural Plausibility Without Binding Specificity: Limits of AI-Based Antibody-Antigen Structure Prediction Confidence ScoresPreprint
Smorodina, E., Ali, M., Kropivšek, K., Salicari, L., Miklavc, S., Kappassov, A., Fu, C., Sormanni, P., de Marco, A., & Greiff, V. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.02.709004 · Cited by 12
Bypassing the Need for Cell Permeabilization: Nanobody CDR3 Peptide Improves Binding on Living Bacteria
Breine, A., holsbeeck, K. V., Martin, C., González, S., Mannes, M., Pardon, E., Steyaert, J., Remaut, H. K., Ballet, S., & der Henst, C. V. (2023) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.3c00116 · Cited by 11
Development of a double antibody sandwich ELISA method for the quantitative detection of serum C-reactive protein based on nanobody
Liu, X., Wang, C., Bai, Y., Wang, W., Han, Y., Cai, S., An, J., & Qu, G. (2024) · Microbial Pathogenesis · doi:10.1016/j.micpath.2024.106615 · Cited by 11
Characterising nanobody developability to improve therapeutic design using the Therapeutic Nanobody Profiler
Gordon, G. L., Gervásio, J. H. D. B., Souders, C., & Deane, C. M. (2026) · Communications Biology · doi:10.1038/s42003-026-09594-y · Cited by 11
Targeting Ras-binding domain of ELMO1 by computational nanobody design
Tam, C., Kukimoto‐Niino, M., Miyata-Yabuki, Y., Tsuda, K., Mishima-Tsumagari, C., Ihara, K., Inoue, M., Yonemochi, M., Hanada, K., Matsumoto, T., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04657-w · Cited by 11
Peptide barcoding for one-pot evaluation of sequence–function relationships of nanobodies
Matsuzaki, Y., Aoki, W., Miyazaki, T., Aburaya, S., Ohtani, Y., Kajiwara, K., Koike, N., Minakuchi, H., Miura, N., Kadonosono, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-01019-6 · Cited by 11
A single-domain antibody library based on a stability-engineered human VH3 scaffold
Lee, N. J., Jung, M., Yang, H. Y., & Shim, H. (2024) · Scientific Reports · doi:10.1038/s41598-024-68680-5 · Cited by 10
The role of electrochemical biosensors in monitoring Apolipoprotein B-100 as a diagnostic tool for cardiovascular disease
Ranjbari, S., Almahmeed, W. A., Kesharwani, P., & Sahebkar, A. (2024) · Microchemical Journal · doi:10.1016/j.microc.2024.111867 · Cited by 9
Confidence scoring for deep learning-predicted antibody–antigen complexes: AntiConf as a precision-driven metric
Ünsal, S., Holland, B., Sardag, I., & Timuçin, E. (2026) · Briefings in Bioinformatics · doi:10.1093/bib/bbag137 · Cited by 10
An artificial neural network model to predict structure-based protein–protein free energy of binding from Rosetta-calculated properties
Ferraz, M. V. F., Neto, J. C. S., Lins, R. D., & Teixeira, E. S. (2023) · Physical Chemistry Chemical Physics · doi:10.1039/d2cp05644e · Cited by 9
A selection and optimization strategy for single-domain antibodies targeting the PHF6 linear peptide within the tau intrinsically disordered protein
Mortelecque, J., Zejneli, O., Bégard, S., Simões, M. C., Hajjar, L. E., Nguyen, M., Cantrelle, F., Hanoulle, X., Rain, J., Colin, M., et al. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107163 · Cited by 9
Paratope Duality and Gullying are Among the Atypical Recognition Mechanisms Used by a Trio of Nanobodies to Differentiate Ebolavirus Nucleoproteins
Sherwood, L. J., Taylor, A. B., Hart, P. J., & Hayhurst, A. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.005 · Cited by 9
Production of Single-Domain Antibodies in Pichia pastoris
Matsuzaki, Y., Kajiwara, K., Aoki, W., & Ueda, M. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2075-5_9 · Cited by 9
Branched Polyethylenimine as a Carrier for Significantly Improving the Biopanning Efficiency of Phages Specific to Hapten
Liu, C., Han, X., Li, G., Zhang, T., Chen, Y., Cao, L., Lin, H., & Sui, J. (2022) · ACS Applied Polymer Materials · doi:10.1021/acsapm.2c00691 · Cited by 9
Structural insights into the role and targeting of EGFRvIII
Bagchi, A., Stayrook, S. E., Xenaki, K. T., Starbird, C. A., Doulkeridou, S., el Khoulati, R., Roovers, R. C., Schmitz, K. R., Henegouwen, P. M. P. V. B. E., & Ferguson, K. M. (2024) · Structure · doi:10.1016/j.str.2024.05.018 · Cited by 8
Nanobodies: A Promising Toolkit for Diagnostic Applications
Wu, W., Ali, A., Sun, L., Hu, J., Hameed, L., Shafi, S., Raza, A., Dinislam, K., Xing, W., Rong, L., et al. (2026) · SmartMat · doi:10.1002/smm2.70088 · Cited by 8
Conformational features and interaction mechanisms of VHH antibodies with β‐hairpin CDR3 : A case of Nb8‐HigB2 interaction
Yamamoto, K., Nagatoishi, S., Matsunaga, R., Nakakido, M., Kuroda, D., & Tsumoto, K. (2023) · Protein Science · doi:10.1002/pro.4827 · Cited by 8
In vitro inhibition of cancer angiogenesis and migration by a nanobody that targets the orphan receptor Tie1
Meltzer, M., Eliash, N., Azoulay, Z., Hadad, U., & Papo, N. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04336-9 · Cited by 8
Designing stable humanized antibodies
Hummer, A. M., & Deane, C. M. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01168-1 · Cited by 8
Nanobody CAR-T cells in cancer: From molecular design to clinical translation
Eisa, A. R., Razavi, F. T., Hoseinzadeh, A., Haghmorad, D., & Baharlou, R. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118819 · Cited by 7
Applications of High-Throughput DNA Sequencing to Single-Domain Antibody Discovery and Engineering
Lowden, M. J., Lei, E. K., Hussack, G., & Henry, K. A. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3381-6_26 · Cited by 7
Single-chain dimers from de novo immunoglobulins as robust scaffolds for multiple binding loops
Roel‐Touris, J., Nadal, M., & Marcos, E. (2023) · Nature Communications · doi:10.1038/s41467-023-41717-5 · Cited by 7
Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library
Ribeiro, R., Moreira, J. N., & Gonçalves, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-61230-z · Cited by 7
Enthalpy‐ versus Entropy‐Driven Molecular Recognition in the Era of Biologics
Varese, M., Guardiola, S., García, J., & Giralt, E. (2019) · ChemBioChem · doi:10.1002/cbic.201900270 · Cited by 7
Development of a synthetic library of humanized nanobodies for targeted IL-6 inhibition
Wang, L., Dong, J., Wu, C., Yan, C., Bi, C., Xu, C., Wu, Y., Zheng, W., & Xing-yuan, M. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1440150 · Cited by 6
Nanobody-as versatile tool emerging in autoimmune diseases
Wang, L., Luo, R., Zhang, W., Jiang, H., Yu, Y., Zhou, W., Zhang, F., Ma, J., & Mei, L. (2024) · Smart Materials in Medicine · doi:10.1016/j.smaim.2024.10.003 · Cited by 6
Affinity‐stability trade‐off mechanism of residue 35 in framework region 2 of VHH antibodies with β‐hairpin CDR3
Yamamoto, K., Nagatoishi, S., Matsunaga, R., Nakakido, M., Kuroda, D., & Tsumoto, K. (2025) · Protein Science · doi:10.1002/pro.70095 · Cited by 6
Coevolved Canonical Loops Conformations of Single-Domain Antibodies: A Tale of Three Pockets Playing Musical Chairs
Gaudreault, F., Corbeil, C. R., Purisima, E. O., & Sulea, T. I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.884132 · Cited by 6
Molecular engineering of nanobodies as tools in allergology: diagnostics and beyond
Aagaard, J. B., Ballegaard, A. R., Ommen, P., & Spillner, E. (2023) · Allergo Journal International · doi:10.1007/s40629-023-00261-w · Cited by 6
Site-Specific Fluorescent Labeling, Single-Step Immunocytochemistry, and Delivery of Nanobodies into Living Cells
Gettemans, J. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2075-5_19 · Cited by 6
Role of the non‐hypervariable FR3 D‐E loop in single‐domain antibody recognition of haptens and carbohydrates
Henry, K. A., Hussack, G., Kumaran, J., Gilbert, M., MacKenzie, C. R., Sulea, T. I., & Arbabi‐Ghahroudi, M. (2019) · Journal of Molecular Recognition · doi:10.1002/jmr.2805 · Cited by 6
Potential and limitations of epitope mapping and molecular targeting in Hymenoptera venom allergy
Fernandes, L. G. R., Spillner, E., & Jakob, T. (2023) · Frontiers in Allergy · doi:10.3389/falgy.2023.1327391 · Cited by 5
Nanobody-based imaging: Advancing precision in molecular diagnostics
Eftekhari, Z., & Kazemi‐Lomedasht, F. (2025) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2025.130884 · Cited by 5

Authors: Zavrtanik, U., Lukan, J., Loris, R., Lah, J., & Hadži, S.
Affiliations: University of Ljubljana (SI)
Statistical Office of the Republic of Slovenia (SI)
Vrije Universiteit Brussel (BE)
Corresponding author: Hadži, San
ORCID: Zavrtanik, Uroš
Lukan, Junoš
Loris, Remy
Lah, Jurij
Hadži, San
Venue: Journal of Molecular Biology
Publisher: Elsevier BV
Published: 2018-10
Volume: 430
Issue: 21
Pages: 4369-4386
ISSN: 0022-2836 (ISSN-L)
DOI: 10.1016/j.jmb.2018.09.002
OpenAlex: W2891129333
Cited by: 169
References: 87
Citations by year: 2026: 21 · 2025: 25 · 2024: 26 · 2023: 30 · 2022: 22 · 2021: 19 · 2020: 12 · 2019: 14
FWCI: 7.76
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Molecular Biology (publishedVersion)
PubMed (publishedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Funders: Slovenian Research Agency (P1-0201)
Onderzoeksraad of the Vrije Universiteit Brussel (SPR13)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords: nanobodies, heavy-chain antibodies, camelid antibodies, epitope recognition, antibody binding sites, aromatic residues, hydrophobic interactions, CDR loops, binding affinity, solvation entropy, protein-protein interaction, crystal structure
MeSH terms: Camelidae, Animals, Epitopes, Binding Sites, Binding Sites, Antibody, Camelids, New World, Immunoglobulin Heavy Chains, Models, Molecular, Protein Binding, Crystallography, X-Ray, Single-Domain Antibodies

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

Structural Basis of Epitope Recognition by Heavy-Chain Camelid Antibodies

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks