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Hirschl Foundation (DE)"},{"name":"Keck Foundation, New York State"},{"name":"NYC Economic Development Corporation (NYSBC)"},{"name":"Herbert and Ann Siegel"},{"name":"New York State Office of Science, Technology and Academic Research"},{"name":"NIH, USA"},{"name":"Keck Foundation, New York"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alpha\u2010synuclein (\u03b1S) is the primary component of Lewy bodies, the pathological hallmark of Parkinson's Disease. Aggregation of \u03b1S is thought to proceed from a primarily disordered state with nascent secondary structure through intermediate conformations to oligomeric forms and finally to mature amyloid fibrils. Low pH conditions lead to conformational changes associated with increased \u03b1S fibril formation. Here we characterize these structural and dynamic changes using solution state NMR measurements of secondary chemical shifts, relaxation parameters, residual dipolar couplings, and paramagnetic relaxation enhancement. We find that the neutralization of negatively charged side\u2010chains eliminates electrostatic repulsion in the C\u2010terminal tail of \u03b1S and leads to a collapse of this region at low pH. Hydrophobic contacts between the compact C\u2010terminal tail and the NAC (non\u2010amyloid\u2010\u03b2 component) region are maintained and may lead to the formation of a globular domain. Transient long\u2010range contacts between the C\u2010terminus of the protein and regions N\u2010terminal to the NAC region are also preserved. Thus, the release of long\u2010range contacts does not play a role in the increased aggregation of \u03b1S at low pH, which we instead attribute to the increased hydrophobicity of the protein.<\/jats:p>","DOI":"10.1002\/pro.149","type":"journal-article","created":{"date-parts":[[2009,4,29]],"date-time":"2009-04-29T15:58:19Z","timestamp":1241020699000},"page":"1531-1540","source":"Crossref","is-referenced-by-count":92,"title":["Charge neutralization and collapse of the C\u2010terminal tail of alpha\u2010synuclein at low pH"],"prefix":"10.1002","volume":"18","author":[{"given":"Sebastian","family":"McClendon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla 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