Premium
Separation of β 2 ‐microglobulin conformers by high‐field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to electrospray ionisation mass spectrometry
Author(s) -
Borysik Antoni J. H.,
Read Paul,
Little David R.,
Bateman Robert H.,
Radford Sheena E.,
Ashcroft Alison E.
Publication year - 2004
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1613
Subject(s) - chemistry , conformational isomerism , ion mobility spectrometry , mass spectrometry , electrospray ionization , electrospray , folding (dsp implementation) , protein folding , analytical chemistry (journal) , chromatography , molecule , organic chemistry , biochemistry , electrical engineering , engineering
An investigation into the use of high‐field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to electrospray ionisation mass spectrometry (ESI‐MS) for the differentiation of co‐populated protein conformers has been conducted on the amyloidogenic protein β 2 ‐microglobulin ( β 2 m). Accumulation of β 2 m in vivo can result in the deposition of insoluble fibrils whose formation is thought to originate from partially folded protein conformers; hence, the folding properties of β 2 m are of significant interest. We have analysed β 2 m using ESI‐FAIMS‐MS under a range of pH conditions and have studied the effect of the ion mobility spectrometry parameters on the behaviour of the various protein conformers. The data show that different protein conformers can be detected and analysed by ESI‐FAIMS‐MS, the results being consistent with observations of pH denaturation obtained using complementary biophysical techniques. A variant of β 2 m with different folding characteristics has been analysed for comparison, and the distinctions observed in the data sets for the two proteins are consistent with their folding behaviour. ESI‐FAIMS‐MS offers significant opportunities for the study of the conformational properties of proteins and thus may present valuable insights into the roles that different conformers play in diseases related to protein folding. Copyright © 2004 John Wiley & Sons, Ltd.