The first N-terminal amino acids of alpha-synuclein are essential for alpha-helical structure formation in vitro and membrane binding in yeast.

ABSTRACT: Alpha-synuclein (alpha-syn), a protein implicated in Parkinson's disease, is structurally diverse. In addition to its random-coil state, alpha-syn can adopt an alpha-helical structure upon lipid membrane binding or a beta-sheet structure upon aggregation. We used yeast biology and in vitro biochemistry to detect how sequence changes alter the structural propensity of alpha-syn. The N-terminus of the protein, which adopts an alpha-helical conformation upon lipid binding, is essential for membrane binding in yeast, and variants that are more prone to forming an alpha-helical structure in vitro are generally more toxic to yeast. beta-Sheet structure and inclusion formation, on the other hand, appear to be protective, possibly by sequestering the protein from the membrane. Surprisingly, sequen

SUBMITTER: Vamvaca K 

PROVIDER: S-EPMC2801807 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature