Relating gas phase to solution conformations: Lessons from disordered proteins.
In recent years both mass spectrometry (MS) and ion mobility mass spectrometry (IM-MS) have been developed as techniques with which to study proteins that lack a fixed tertiary structure but may contain regions that form secondary structure elements transiently, namely intrinsically disordered proteins (IDPs). IM-MS is a suitable method for the study of IDPs which provides an insight to conformations that are present in solution, potentially enabling the analysis of lowly populated structural forms. Here, we describe the IM-MS data of two IDPs; α-Synuclein (α-Syn) which is implicated in Parkinson's disease, and Apolipoprotein C-II (ApoC-II) which is involved in cardiovascular diseases. We report an apparent discrepancy in the way that ApoC-II behaves in the gas phase. While most IDPs, including α-Syn, present in many charge states and a wide range of rotationally averaged collision cross sections (CCSs), ApoC-II presents in just four charge states and a very narrow range of CCSs, independent of solution conditions. Here, we compare MS and IM-MS data of both proteins, and rationalise the differences between the proteins in terms of different ionisation processes which they may adhere to.
The Michael Barber Centre for Collaborative Mass Spectrometry, The School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK.
Rebecca
R
Beveridge
The Michael Barber Centre for Collaborative Mass Spectrometry, The School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK.
Ashley S
AS
Phillips
Waters Corporation, Wilmslow, UK.
Laetitia
L
Denbigh
The Michael Barber Centre for Collaborative Mass Spectrometry, The School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK.
Hassan M
HM
Saleem
School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
Cait E
CE
MacPhee
The Michael Barber Centre for Collaborative Mass Spectrometry, The School of Chemistry, Manchester Institute for Biotechnology, University of Manchester, Manchester, UK.
Perdita E
PE
Barran
D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D041961:Deuterium Exchange Measurement / Q000379:methods*; D005740:Gases; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000032:analysis* / Q000737:chemistry*; D008969:Molecular Sequence Data; D010300:Parkinson Disease; D011487:Protein Conformation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D051844:alpha-Synuclein
D053304:Apolipoprotein C-II; D005740:Gases; D064267:Intrinsically Disordered Proteins; D051844:alpha-Synuclein
Electrospray Ionization Mechanisms; HDX-MS; Ion Mobility Mass Spectrometry; Parkinson's disease; Technology