title: Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment.
abstract: Some pathogenic mutations associated with Alzheimer's disease are thought to affect structural-dynamic properties and the lateral dimerization of amyloid precursor protein (APP) in neuron membrane. Dimeric structure of APP transmembrane fragment Gln(686)-Lys(726) was determined in membrane-mimicking dodecylphosphocholine micelles using high-resolution NMR spectroscopy. The APP membrane-spanning α-helix Lys(699)-Lys(724) self-associates in a left-handed parallel dimer through extended heptad repeat motif I(702)X(3)M(706)X(2)G(709)X(3)A(713)X(2)I(716)X(3)I(720)X(2)I(723), whereas the juxtamembrane region Gln(686)-Val(695) constitutes the nascent helix, also sensing the dimerization. The dimerization mechanism of APP transmembrane domain has been described at atomic resolution for the first time and is important for understanding molecular events of APP sequential proteolytical cleavage resulting in amyloid-β peptide.
authors.affiliation: Division of Structural Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Str. Miklukho-Maklaya 16/10, Moscow 117997, Russian Federation.
authors.forename: Kirill D
authors.initials: KD
authors.lastname: Nadezhdin
authors.forename: Olga V
authors.initials: OV
authors.lastname: Bocharova
authors.forename: Eduard V
authors.initials: EV
authors.lastname: Bocharov
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Arseniev
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008823:Micelles; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D016564:Amyloid beta-Protein Precursor; D008567:Membranes, Artificial; D008823:Micelles