Bleiholder Christian, Bowers Michael T
Department of Chemistry and Biochemistry, Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306; email:
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106.
Annu Rev Anal Chem (Palo Alto Calif). 2017 Jun 12;10(1):365-386. doi: 10.1146/annurev-anchem-071114-040304. Epub 2017 Mar 24.
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.
离子淌度质谱（IMS-MS）方法越来越多地用于研究肽和蛋白质的非共价组装体。本综述聚焦于氨基酸和肽的非共价自组装，这些体系是淀粉样蛋白过程的核心，在许多毁灭性疾病中起着关键作用。详细讨论了三种不同的体系：与阿尔茨海默病病因相关的42个残基的肽淀粉样β-蛋白42、几种具有6-11个残基的淀粉样形成肽以及单个氨基酸的组装。我们还从更基础的角度讨论了在IMS-MS测量中当分析物离子的溶剂被去除时，决定蛋白质及其组装体变性速度的过程，以及如何使测量变得温和以便能够记录具有生物学意义的数据。
