ArticleThe journal of physical chemistry. B2013
A nanobody binding to non-amyloidogenic regions of the protein human lysozyme enhances partial unfolding but inhibits amyloid fibril formation.
Article in The journal of physical chemistry. B, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 46 citations in OpenAlex.
- Tiny tools closing the gap: nanobodies in research and therapy.Function (Oxford, England) · 2026Review
- Highly potent multivalent VHH antibodies against Chikungunya isolated from an alpaca naïve phage display library.Journal of nanobiotechnology · 2022Article
- Single Molecule Characterization of Amyloid Oligomers.Molecules (Basel, Switzerland) · 2021Review
- Nanobodies targeting immune checkpoint molecules for tumor immunotherapy and immunoimaging (Review).International journal of molecular medicine · 2021Review
- Nanobodies against the metal binding domains of ATP7B as tools to study copper transport in the cell.Metallomics : integrated biometal science · 2020Article
- ModiBodies: A computational method for modifying nanobodies in nanobody-antigen complexes to improve binding affinity and specificity.Journal of biological physics · 2020Article
- Reflections on professor Sir Christopher M. Dobson (1949-2019).Biophysical reviews · 2020Article
- The structural basis of nanobody unfolding reversibility and thermoresistance.Scientific reports · 2018Article
- Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.Angewandte Chemie (International ed. in English) · 2018Review
- Elucidating the Inhibitory Potential of Designed Peptides Against Amyloid Fibrillation and Amyloid Associated Cytotoxicity.Frontiers in chemistry · 2018Article
- Exploiting sequence and stability information for directing nanobody stability engineering.Biochimica et biophysica acta. General subjects · 2017Article
- Nanobodies raised against monomeric ɑ-synuclein inhibit fibril formation and destabilize toxic oligomeric species.BMC biology · 2017Article
- The Significance of the Location of Mutations for the Native-State Dynamics of Human Lysozyme.Biophysical journal · 2016Article
- Nanobodies as Probes for Protein Dynamics in Vitro and in Cells.The Journal of biological chemistry · 2016Review
- Structure of a single-chain Fv bound to the 17 N-terminal residues of huntingtin provides insights into pathogenic amyloid formation and suppression.Journal of molecular biology · 2015Article
- Fully Human VH Single Domains That Rival the Stability and Cleft Recognition of Camelid Antibodies.The Journal of biological chemistry · 2015Article
- Class A β-lactamases as versatile scaffolds to create hybrid enzymes: applications from basic research to medicine.BioMed research international · 2013Review
- Review
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14 authors at 5 institutions in 5 countries.
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Abstract
We report the effects of the interaction of two camelid antibody fragments, generally called nanobodies, namely cAb-HuL5 and a stabilized and more aggregation-resistant variant cAb-HuL5G obtained by protein engineering, on the properties of two amyloidogenic variants of human lysozyme, I56T and D67H, whose deposition in vital organs including the liver, kidney, and spleen is associated with a familial non-neuropathic systemic amyloidosis. Both NMR spectroscopy and X-ray crystallographic studies reveal that cAb-HuL5 binds to the α-domain, one of the two lobes of the native lysozyme structure. The binding of cAb-HuL5/cAb-HuL5G strongly inhibits fibril formation by the amyloidogenic variants; it does not, however, suppress the locally transient cooperative unfolding transitions, characteristic of these variants, in which the β-domain and the C-helix unfold and which represents key early intermediate species in the formation of amyloid fibrils. Therefore, unlike two other nanobodies previously described, cAb-HuL5/cAb-HuL5G does not inhibit fibril formation via the restoration of the global cooperativity of the native structure of the lysozyme variants to that characteristic of the wild-type protein. Instead, it inhibits a subsequent step in the assembly of the fibrils, involving the unfolding and structural reorganization of the α-domain. These results show that nanobodies can protect against the formation of pathogenic aggregates at different stages in the structural transition of a protein from the soluble native state into amyloid fibrils, illustrating their value as structural probes to study the molecular mechanisms of amyloid fibril formation. Combined with their amenability to protein engineering techniques to improve their stability and solubility, these findings support the suggestion that nanobodies can potentially be developed as therapeutics to combat protein misfolding diseases.
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