title: Dimethylsulfoxide-quenched hydrogen/deuterium exchange method to study amyloid fibril structure.
abstract: A general method to analyze the structure of a supramolecular complex of amyloid fibrils at amino acid residue resolution has been developed. This method combines the NMR-detected hydrogen/deuterium (H/D) exchange technique to detect hydrogen-bonded amide groups and the ability of the aprotic organic solvent dimethylsulfoxide (DMSO) to dissolve amyloid fibrils into NMR-observable, monomeric components while suppressing the undesired H/D exchange reaction. Moreover, this method can be generally applied to amyloid fibrils to elucidate the distribution of hydrogen-bonded amino acid residues in the three-dimensional molecular organization in the amyloid fibrils. In this study, we describe theoretical considerations in the H/D exchange method to obtain the structural information of proteins, and the DMSO-quenched H/D exchange method to study a supramolecular complex of amyloid fibrils. A possible application of this method to study the interaction of a protein/peptide with phospholipid membrane is also discussed.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi, Kyoto 606-8501, Japan. hoshi@pharm.kyoto-u.ac.jp
authors.forename: Masaru
authors.initials: M
authors.lastname: Hoshino
authors.forename: Hidenori
authors.initials: H
authors.lastname: Katou
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D003903:Deuterium / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D019906:Nuclear Magnetic Resonance, Biomolecular; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism
chemical_list: D000682:Amyloid; D010743:Phospholipids; D006859:Hydrogen; D003903:Deuterium; D004121:Dimethyl Sulfoxide