title: NMR mapping of copper binding sites in alpha-synuclein.
abstract: Copper binding to the Parkinson disease-linked protein alpha-synuclein (aS) has been shown to accelerate its oligomerization in vitro and may therefore play a role in aS-mediated pathology in vivo. We use NMR spectroscopy to identify a number of independent copper binding sites in both the lipid-binding N-terminal domain and the highly acidic C-terminal domain of aS. Most of the sites appear to involve negatively charged amino acid side chains, but binding is also observed to the sole histidine residue located at position 50 and to the N-terminal amino group. Both the N-terminal and the histidine sites, as well as the sites in the C-terminal tail, can also bind copper in the more highly structured conformation adopted by aS upon binding to detergent micelles or lipid vesicles. There is no evidence for the formation of any sites requiring long-range order in the protein.
authors.affiliation: Department of Biochemistry and Program in Structural Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
authors.forename: Yoon-Hui
authors.initials: YH
authors.lastname: Sung
authors.forename: Carla
authors.initials: C
authors.lastname: Rospigliosi
authors.forename: David
authors.initials: D
authors.lastname: Eliezer
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D003902:Detergents; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008081:Liposomes; D008823:Micelles; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D003902:Detergents; D008081:Liposomes; D008823:Micelles; D011994:Recombinant Proteins; D051844:alpha-Synuclein; D003300:Copper