Collision induced unfolding coupled with gas-phase hydrogen/deuterium exchange give evidence for highly zwitterionic proteins in the gas phase

The net charge of a natively folded electrosprayed protein can be accurately predicted from the protein size. How charges are distributed on a protein – the charge configuration – is still a challenge however, both to determine experimentally and to predict from theory and computations, hampering both modelling and interpretation of native mass spectrometry experiments. Here, a combination of molecular dynamics simulations and experiments, including a novel conjunction of collision induced unfolding and gas-phase hydrogen/deuterium exchange, were used on a set of engineered proteins differing in their surface chemistry to general principles underpinning the charge configurations. Testing three charging models against simulations and experiments, only the highly zwitterionic model passed falsification efforts. Our results are consistent with the notion of the proteins being partially kinetically trapped in a charge configuration inherited from solution.

NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
mass spectrometry
molecular dynamics
electrospray ionisation
protein
proton transfer
gas-phase hydrogen/deuterium exchange
collision induced unfolding
Biokemi
Biochemistry

Chandler, Shane A (author)
Allison, Timothy M (author)
Mize, Todd H (author)
Mistarz, Ulrik H (author)
Rand, Kasper D (author)
Marklund, Erik GUppsala universitet,Biokemi,Marklund group(Swepub:uu)ermar499 (author)
Benesch, Justin L P (author)
Uppsala universitetBiokemi (creator_code:org_t)

By the author/editor: Costeira-Paulo, ...; Chandler, Shane ...; Allison, Timothy ...; Mize, Todd H; Mistarz, Ulrik H; Rand, Kasper D; show more...; Marklund, Erik G; Benesch, Justin ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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