{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:27:21Z","timestamp":1784395641876,"version":"3.55.0"},"reference-count":82,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This article presents experimental evidence and computed molecular models of a potential interaction between receptor domain D5 of TrkB with the carboxyl-terminal domain of tetanus neurotoxin (Hc-TeNT). Computational simulations of a novel small cyclic oligopeptide are designed, synthesized, and tested for possible tetanus neurotoxin-D5 interaction. A hot spot of this protein-protein interaction is identified in analogy to the hitherto known crystal structures of the complex between neurotrophin and D5. Hc-TeNT activates the neurotrophin receptors, as well as its downstream signaling pathways, inducing neuroprotection in different stress cellular models. Based on these premises, we propose the Trk receptor family as potential proteic affinity receptors for TeNT. In vitro, Hc-TeNT binds to a synthetic TrkB-derived peptide and acts similar to an agonist ligand for TrkB, resulting in phosphorylation of the receptor. These properties are weakened by the mutagenesis of three residues of the predicted interaction region in Hc-TeNT. It also competes with Brain-derived neurotrophic factor, a native binder to human TrkB, for the binding to neural membranes, and for uptake in TrkB-positive vesicles. In addition, both molecules are located together in vivo at neuromuscular junctions and in motor neurons.<\/jats:p>","DOI":"10.3390\/molecules26133988","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T02:16:34Z","timestamp":1625019394000},"page":"3988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Interaction between a Novel Oligopeptide Fragment of the Human Neurotrophin Receptor TrkB Ectodomain D5 and the C-Terminal Fragment of Tetanus Neurotoxin"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5003-3789","authenticated-orcid":false,"given":"Ana","family":"Candalija","sequence":"first","affiliation":[{"name":"Molecular Biology Department, Institut de Neruoci\u00e8nces and Biochemistry, Medicine Faculty, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-2682","authenticated-orcid":false,"given":"Thomas","family":"Scior","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Sciences, BUAP, Puebla 72000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Richard","family":"Rackwitz","sequence":"additional","affiliation":[{"name":"Peptide Specialities Laboratory, Im Neuenheimer Feld, Univerisity Campus, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan E.","family":"Ruiz-Castelan","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Sciences, BUAP, Puebla 72000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ygnacio","family":"Martinez-Laguna","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Sciences, BUAP, Puebla 72000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-8034","authenticated-orcid":false,"given":"Jos\u00e9","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Molecular Biology Department, Institut de Neruoci\u00e8nces and Biochemistry, Medicine Faculty, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Neurodegenerative Diseases (CIBERNED), 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6883","DOI":"10.3390\/ijms13066883","article-title":"Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway","volume":"13","author":"Calvo","year":"2012","journal-title":"Int. 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