title: Spin labeling analysis of amyloids and other protein aggregates.
abstract: Because of the enormous size of amyloid fibrils and their low tendency to form crystal lattices, it has been difficult to obtain high-resolution structural information on these aggregates. Magnetic resonance methods, such as solid-state nuclear magnetic resonance spectroscopy and electron paramagnetic resonance (EPR) spectroscopy, are promising new technologies by which to obtain molecular models. This chapter will focus on the application of EPR spectroscopy to amyloids and other protein aggregates. Site-directed spin labeling (SDSL), in combination with EPR spectroscopy, has been successfully used to study protein structure and the dynamics of soluble as well as membrane proteins. Recent studies indicate that this strategy is also well suited for studying amyloid fibrils. For example, an important outcome of the SDSL studies performed in our laboratory is that fibrils of amyloid beta, islet amyloid polypeptide, alpha-synuclein, and tau have their beta-strands aligned in an in-register, parallel fashion. Future studies promise to yield molecular information about fibril topography and protofilament arrangement and can be extended to include oligomeric structures.
authors.affiliation: University of Southern California, Department of Biochemistry and Molecular Biology, Los Angeles, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Margittai
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D008698:Mesylates / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D013113:Spin Labels; D016875:tau Proteins / Q000737:chemistry
chemical_list: D000682:Amyloid; D003497:Cyclic N-Oxides; D008698:Mesylates; D013113:Spin Labels; D016875:tau Proteins; C034248:(1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate; D003545:Cysteine