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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation. | | [https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation. |
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| == Publication Abstract from PubMed ==
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| Nanobodies are single-domain fragments of antibodies with comparable specificity and affinity to antibodies. They are emerging as versatile tools in biology due to their relatively small size. Here, we report the crystal structure of a specific nanobody Nbalpha-syn01, bound to a 14 amino acid long peptide of alpha-synuclein (alphaSyn), a 140-residue protein whose aggregation is associated with Parkinson's disease. The complex structure exhibits a unique binding pattern where the alphaSyn peptide replaces the N-terminal region of nanobody. Recognition is mediated principally by extended main chain interaction of the alphaSyn peptide and specificity of the interaction lies in the central 48-52 region of alphaSyn peptide. Structure-guided truncation of Nbalpha-syn01 shows tighter binding to alphaSyn peptide and improved inhibition of alpha-synuclein aggregation. The structure of the truncated complex was subsequently determined and was indistinguishable to full length complex as the full-length form had no visible electron density for the N-terminal end. These findings reveal the molecular basis for a previously unobserved binding mode for nanobody recognition of alpha-synuclein, providing an explanation for the enhanced binding, and potential for an alternate framework for structure-based protein engineering of nanobodies to develop better diagnostic and therapeutic tools. This article is protected by copyright. All rights reserved.
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| Structural insights into the unique recognition module between alpha-synuclein peptide and nanobody.,Islam Z, Vaikath NN, Hmila I, El-Agnaf OMA, Kolatkar PR Protein Sci. 2023 Dec 17:e4875. doi: 10.1002/pro.4875. PMID:38105512<ref>PMID:38105512</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| <div class="pdbe-citations 8jjv" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |