The Solution Assembly of Biological Molecules Using Ion Mobility Methods: From Amino Acids to Amyloid β-Protein

• Published in: Annual review of analytical chemistry (Palo Alto, Calif.) Calif.), 2017-06, Vol.10 (1), p.365-386
• Main Authors: Bleiholder, Christian, Bowers, Michael T
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino acids; Amino Acids - chemistry; Amino Acids - metabolism; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; amyloid formation; Assemblies; Etiology; Humans; ion mobility spectrometry; Ionic mobility; Ions; Ions - chemistry; Mass spectrometry; Mass spectroscopy; Microscopy, Atomic Force; Mobility; Neurodegenerative diseases; Peptides; Peptides - chemistry; Peptides - metabolism; Protein Folding; protein self-assembly; Protein Structure, Tertiary; Proteins; Scientific imaging; Self-assembly; Spectrometry, Mass, Electrospray Ionization; Spectroscopy; β-Amyloid
• ISSN: 1936-1327; 1936-1335
• DOI: 10.1146/annurev-anchem-071114-040304

Ion mobility spectrometry-mass spectrometry (IMS-MS) methods are increasingly used to study noncovalent assemblies of peptides and proteins. This review focuses on the noncovalent self-assembly of amino acids and peptides, systems at the heart of the amyloid process that play a central role in a number of devastating diseases. Three different systems are discussed in detail: the 42-residue peptide amyloid-β42 implicated in the etiology of Alzheimer's disease, several amyloid-forming peptides with 6-11 residues, and the assembly of individual amino acids. We also discuss from a more fundamental perspective the processes that determine how quickly proteins and their assemblies denature when the analyte ion has been stripped of its solvent in an IMS-MS measurement and how to soften the measurement so that biologically meaningful data can be recorded.