{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:11:40Z","timestamp":1791295900583,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":762,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The synucleins are a family of intrinsically disordered proteins involved in various human diseases. \u03b1\u2010Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while \u03b3\u2010synuclein is overexpressed in a majority of late\u2010stage breast cancers. Despite fairly strong sequence similarity between the amyloid\u2010forming regions of \u03b1\u2010 and \u03b3\u2010synuclein, \u03b3\u2010synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of \u03b1\u2010 and \u03b3\u2010synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for \u03b3\u2010synuclein and compared them to previously published shifts for \u03b1\u2010synuclein. In order to facilitate direct comparison, we have implemented a simple new technique for re\u2010referencing chemical shifts that we have found to be highly effective for both disordered and folded proteins. In addition, we have developed a new method that combines different chemical shifts into a single residue\u2010specific secondary structure propensity (SSP) score. We observe significant differences between \u03b1\u2010 and \u03b3\u2010synuclein secondary structure propensities. Most interestingly, \u03b3\u2010synuclein has an increased \u03b1\u2010helical propensity in the amyloid\u2010forming region that is critical for \u03b1\u2010synuclein fibrillation, suggesting that increased structural stability in this region may protect against \u03b3\u2010synuclein aggregation. This comparison of residue\u2010specific secondary structure propensities between intrinsically disordered homologs highlights the sensitivity of transient structure to sequence changes, which we suggest may have been exploited as an evolutionary mechanism for fast modulation of protein structure and, hence, function.<\/jats:p>","DOI":"10.1110\/ps.062465306","type":"journal-article","created":{"date-parts":[[2006,11,6]],"date-time":"2006-11-06T20:30:38Z","timestamp":1162845038000},"page":"2795-2804","source":"Crossref","is-referenced-by-count":769,"title":["Sensitivity of secondary structure propensities to sequence differences between \u03b1\u2010 and \u03b3\u2010synuclein: Implications for fibrillation"],"prefix":"10.1002","volume":"15","author":[{"given":"Joseph A.","family":"Marsh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay 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