Gas‐phase conformations of intrinsically disordered proteins and their complexes with ligands: Kinetically trapped states during transfer from solution to the gas phase

Abstract

Flexible structures of intrinsically disordered proteins (IDPs) are crucial for versatile functions in living organisms, which involve interaction with diverse partners. Electrospray ionization ion mobility mass spectrometry (ESI‐IM‐MS) has been widely applied for structural characterization of apo‐state and ligand‐associated IDPs via two‐dimensional separation in the gas phase. Gas‐phase IDP structures have been regarded as kinetically trapped states originated from conformational features in solution. However, an implication of the states remains elusive in the structural characterization of IDPs, because it is unclear what structural property of IDPs is preserved. Recent studies have indicated that the conformational features of IDPs in solution are not fully reproduced in the gas phase. Nevertheless, the molecular interactions captured in the gas phase amplify the structural differences between IDP conformers. Therefore, an IDP conformational change that is not observed in solution is observable in the gas‐phase structures obtained by ESI‐IM‐MS. Herein, we have presented up‐to‐date researches on the key implications of kinetically trapped states in the gas phase with a brief summary of the structural dynamics of IDPs in ESI‐IM‐MS.

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“…All CsgA homologs namely, EC CsgA, HA CsgA, CY CsgA, and CD CsgA, showed typical mass spectrum for intrinsically disordered protein with a wide range of charge states from 5+ to 26+ ( Fig. 5 , A – F ) ( 55 , 56 , 57 ). Interestingly, using IM-MS, we observed two distinct populations of monomeric and dimeric CsgA species being present with each of the homolog ( Fig.…”

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“…Ion mobility mass spectrometry (IM-MS) coupled with electrospray ionization (ESI) enables the characterization of ion structures in the gas phase. − The experimental collisional cross section (CCS) supported by theoretical three-dimensional modeling is the principal means of characterizing gas-phase ion structures. Electrostatic interactions, which are substantially moderated in high dielectric solvents such as water, dominate protein structures in the gas phase. , Thus, the question of whether gas-phase protein structures correlate with those in solution has been widely investigated . The loss of water molecules may disrupt the balance between hydration and intramolecular protein interactions during transfer of proteins from solution to the gas phase.…”

“…ESI-IM-MS has also been used to probe protein assemblies and to obtain geometric information on protein complexes. ,,, The low permittivity of the gas phase may strengthen noncovalent interactions originating in the solvent and magnify their structural influence. , For example, human islet amyloid polypeptide (hIAPP) prefers a compact conformer with Cu­(II) that is retained upon transfer to the gas phase from solution . In contrast, proteins bound to other metal ions (Ca 2+ , Mg 2+ , 2Na + ) adopt an extended conformation because of electrostatic repulsions in the gas phase .…”