title: Structure of interacting segments in the growing amyloid fibril of beta2-microglobulin probed with IR spectroscopy.
abstract: Inter-segmental interaction at the growing tip of the amyloid fibril of beta2-microglobulin (beta2m) was investigated using IR microscopy. Cross-seeded fibril formation was implemented, in which the amyloid fibril of the #21-31 fragment of beta2m (fA[#21-31]) was generated on the beta2m amyloid fibril (fA[beta2m]) as a seed. Differences between the IR spectra of the cross-seeded fibril and those of the seed were attributed to the contribution from the tip, whose structure is discussed. The results indicated that 6.5 +/- 1.0 out of 11 residues of the fA[#21-31] tip on fA[beta2m] are contained in a beta-sheet at pH 2.5, which was smaller than the corresponding value (7.5 +/- 1.1 residues) of the spontaneous fA[#21-31] at pH 2.5. The tip was suggested to have a planar structure, indicating the planarity of the interacting segment. The N-terminal region of fA[#21-31] in the fibril is more exposed to the solvent than that in the tip, and vice versa for the C-terminal region. This is consistent with the different protonation levels of these regions, and the direction of peptide in the fibrils is determined from these results.
authors.affiliation: Department of Photoscience, School of Advanced Studies, The Graduate University for Advanced Studies, Shonan Village, Hayama, Kanagawa, 240-0193, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.forename: Teizo
authors.initials: T
authors.lastname: Kitagawa
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D006801:Humans; D007259:Infrared Rays; D007554:Isotopes / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013057:Spectrum Analysis / Q000379:methods*; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D007554:Isotopes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin