title: A broken alpha -helix in folded alpha -Synuclein.
abstract: alpha-Synuclein is a small cytosolic protein of presynaptic nerve terminals composed of seven 11-residue repeats and a hydrophilic tail. alpha-Synuclein misfolding and dysfunction may contribute to the pathogenesis of Parkinson's disease and neurodegenerative dementias, but its normal folding and function are unknown. In solution, alpha-synuclein is natively unstructured but assumes an alpha-helical conformation upon binding to phospholipid membranes. We now show that this conformation of alpha-synuclein consists of two alpha-helical regions that are interrupted by a short break. The structural organization of the alpha-helices of alpha-synuclein was not anticipated by sequence analyses and may be important for its pathogenic role.
authors.affiliation: Center for Basic Neuroscience, Department of Molecular Genetics, and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA. Sreeganga.Chandra@UTSouthwestern.edu
authors.forename: Sreeganga
authors.initials: S
authors.lastname: Chandra
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Chen
authors.forename: Josep
authors.initials: J
authors.lastname: Rizo
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000595:Amino Acid Sequence; D003902:Detergents / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000209:etiology; D010449:Peptide Mapping; D010743:Phospholipids / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000187:drug effects; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D003902:Detergents; D008081:Liposomes; D009419:Nerve Tissue Proteins; D010743:Phospholipids; D010750:Phosphoproteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein