{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:42:16Z","timestamp":1790703736975,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["243182"],"award-info":[{"award-number":["243182"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intracellular deposits of \u03b1\u2010synuclein in the form of Lewy bodies are major hallmarks of Parkinson's disease (PD) and a range of related neurodegenerative disorders. Post\u2010translational modifications (PTMs) of \u03b1\u2010synuclein are increasingly thought to be major modulators of its structure, function, degradation and toxicity. Among these PTMs, phosphorylation near the C\u2010terminus at S129 has emerged as a dominant pathogenic modification as it is consistently observed to occur within the brain and cerebrospinal fluid (CSF) of post\u2010mortem PD patients, and its level appears to correlate with disease progression. Phosphorylation at the neighboring tyrosine residue Y125 has also been shown to protect against \u03b1\u2010synuclein toxicity in a Drosophila model of PD. In the present study we address the potential roles of C\u2010terminal phosphorylation in modulating the interaction of \u03b1\u2010synuclein with other protein partners, using a single domain antibody fragment (NbSyn87) that binds to the C\u2010terminal region of \u03b1\u2010synuclein with nanomolar affinity. The results reveal that phosphorylation at S129 has negligible effect on the binding affinity of NbSyn87 to \u03b1\u2010synuclein while phosphorylation at Y125, only four residues away, decreases the binding affinity by a factor of 400. These findings show that, despite the fact that \u03b1\u2010synuclein is intrinsically disordered in solution, selective phosphorylation can modulate significantly its interactions with other molecules and suggest how this particular form of modification could play a key role in regulating the normal and aberrant function of \u03b1\u2010synuclein.<\/jats:p>","DOI":"10.1002\/pro.3412","type":"journal-article","created":{"date-parts":[[2018,3,31]],"date-time":"2018-03-31T05:43:54Z","timestamp":1522475034000},"page":"1262-1274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Exploring the role of post\u2010translational modifications in regulating \u03b1\u2010synuclein interactions by studying the effects of phosphorylation on nanobody binding"],"prefix":"10.1002","volume":"27","author":[{"given":"Farah","family":"El Turk","sequence":"first","affiliation":[{"name":"Centre for Mosfolding Diseases, Department of 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