title: Identification and Structural Characterization of the N-terminal Amyloid Core of Orb2 isoform A.
abstract: Orb2 is a functional amyloid that plays a key role in Drosophila long-term memory formation. Orb2 has two isoforms that differ in their N-termini. The N-terminus of the A isoform (Orb2A) that precedes its Q-rich prion-like domain has been shown to be important for Orb2 aggregation and long-term memory. However, besides the fact that it forms fibrillar aggregates, structural information of Orb2 is largely absent. To understand the importance of the N-terminus of Orb2A and its relation to the fibril core, we recorded solid-state NMR and EPR data on fibrils formed by the first 88 residues of Orb2A (Orb2A88). These data show that the N-terminus of Orb2A not only promotes the formation of fibrils, but also forms the fibril core of Orb2A88. This fibril core has an in-register parallel β-sheet structure and does not include the Q-rich, prion-like domain of Orb2. The Q-rich domain is part of the unstructured region, which becomes increasingly dynamic towards the C-terminus.
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Cervantes
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Thalia H
authors.initials: TH
authors.lastname: Bajakian
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Soria
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Falk
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Service
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
authors.affiliation: Department of Biochemistry &Molecular Medicine and the Zilkha Neurogenetic Institute, Keck School of Medicine of USC, 1501 San Pablo St, Los Angeles, CA 90033, USA.
authors.forename: Ansgar B
authors.initials: AB
authors.lastname: Siemer
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D000072417:Protein Domains; D020033:Protein Isoforms; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000682:Amyloid; D029721:Drosophila Proteins; C529066:Orb2 protein, Drosophila; D020033:Protein Isoforms; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors