Ensemble methods enable a new definition for the solution to gas-phase transfer of intrinsically disordered proteins

TY - JOUR

T1 - Ensemble methods enable a new definition for the solution to gas-phase transfer of intrinsically disordered proteins

AU - Borysik, Antoni J

AU - Kovacs, Denes

AU - Guharoy, Mainak

AU - Tompa, Peter

PY - 2015/10/5

Y1 - 2015/10/5

N2 - Intrinsically disordered proteins (IDPs) are important for health and disease process yet their lack of net structure precludes an understanding of their function using classical methods. Gas-phase techniques provide a promising alternative to access information on the structure and dynamics of IDPs, but the fidelity to which these methods reflect the solution conformations of these proteins has been difficult to ascertain. Here we combine current ensemble techniques with a range of other methods to investigate the solution to gas-phase transfer of many different IDPs. We show that IDPs undergo a vast conformational space expansion in the absence of solvent to sample a conformational space 3 - 5 fold broader than in solution. Moreover, we show that this process is coupled to the electrospray ionization process which brings about the generation of additional subpopulations for these proteins not observed in solution; with competing effects on protein charge and shape. Ensemble methods have permitted a new definition of the solution to gas-phase transfer of IDPs and provided a road map for future investigations into flexible systems by mass spectrometry.

AB - Intrinsically disordered proteins (IDPs) are important for health and disease process yet their lack of net structure precludes an understanding of their function using classical methods. Gas-phase techniques provide a promising alternative to access information on the structure and dynamics of IDPs, but the fidelity to which these methods reflect the solution conformations of these proteins has been difficult to ascertain. Here we combine current ensemble techniques with a range of other methods to investigate the solution to gas-phase transfer of many different IDPs. We show that IDPs undergo a vast conformational space expansion in the absence of solvent to sample a conformational space 3 - 5 fold broader than in solution. Moreover, we show that this process is coupled to the electrospray ionization process which brings about the generation of additional subpopulations for these proteins not observed in solution; with competing effects on protein charge and shape. Ensemble methods have permitted a new definition of the solution to gas-phase transfer of IDPs and provided a road map for future investigations into flexible systems by mass spectrometry.

U2 - 10.1021/jacs.5b06027

DO - 10.1021/jacs.5b06027

M3 - Article

C2 - 26437245

SN - 0002-7863

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

ER -