{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:53:57Z","timestamp":1791942837726,"version":"4.3.4"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,2]]},"abstract":"<jats:p>\n                    In idiopathic Parkinson's disease, intracytoplasmic neuronal inclusions (Lewy bodies) containing aggregates of the protein \u03b1-synuclein (\u03b1S) are deposited in the pigmented nuclei of the brainstem. The mechanisms underlying the structural transition of innocuous, presumably natively unfolded, \u03b1S to neurotoxic forms are largely unknown. Using paramagnetic relaxation enhancement and NMR dipolar couplings, we show that monomeric \u03b1S assumes conformations that are stabilized by long-range interactions and act to inhibit oligomerization and aggregation. The autoinhibitory conformations fluctuate in the range of nanoseconds to micro-seconds corresponding to the time scale of secondary structure formation during folding. Polyamine binding and\/or temperature increase, conditions that induce aggregation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , release this inherent tertiary structure, leading to a completely unfolded conformation that associates readily. Stabilization of the native, autoinhibitory structure of \u03b1S constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson's disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0407146102","type":"journal-article","created":{"date-parts":[[2005,1,25]],"date-time":"2005-01-25T22:43:38Z","timestamp":1106693018000},"page":"1430-1435","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":781,"title":["Release of long-range tertiary interactions potentiates aggregation of natively unstructured \u03b1-synuclein"],"prefix":"10.1073","volume":"102","author":[{"given":"Carlos W.","family":"Bertoncini","sequence":"first","affiliation":[{"name":"Departments of Molecular Biology and NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 G\u00f6ttingen, Germany; and Instituto de Biolog\u00eda Molecular y Celular de Rosario, Universidad Nacional de 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