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The sequence region 35\u201359 contains \u03b2\u2010strand segments \u03b21 and \u03b22 of \u03b1\u2010syn amyloid fibril models and most disease\u2010related mutations. \u03b21 and \u03b22 frequently engage in transient interactions in monomeric \u03b1\u2010syn. The consequences of \u03b21\u2013\u03b22 contacts are evaluated by disulfide engineering, biophysical techniques, and cell viability assays. The double\u2010cysteine mutant \u03b1\u2010synCC, with a disulfide linking \u03b21 and \u03b22, is aggregation\u2010incompetent and inhibits aggregation and toxicity of wild\u2010type \u03b1\u2010syn. We show that \u03b1\u2010syn delays the aggregation of amyloid\u2010\u03b2 peptide and islet amyloid polypeptide involved in Alzheimer\u2019s disease and type\u20052 diabetes, an effect enhanced in the \u03b1\u2010synCC mutant. Tertiary interactions in the \u03b21\u2013\u03b22 region of \u03b1\u2010syn interfere with the nucleation of amyloid formation, suggesting promotion of such interactions as a potential therapeutic approach.<\/jats:p>","DOI":"10.1002\/anie.201503018","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T08:57:01Z","timestamp":1435395421000},"page":"8837-8840","source":"Crossref","is-referenced-by-count":28,"title":["Contact between the \u03b21 and \u03b22 Segments of \u03b1\u2010Synuclein that Inhibits Amyloid Formation"],"prefix":"10.1002","volume":"54","author":[{"given":"Hamed","family":"Shaykhalishahi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aziz","family":"Gauhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael M.","family":"W\u00f6rdehoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara S. 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