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Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry
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- Abramsson, Mia L. (author)
- Karolinska Institutet
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- Sahin, Cagla (author)
- Karolinska Institutet
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- Hopper, Jonathan T. S. (author)
- Univ Oxford, Dept Chem, Oxford OX1 3QZ, England.
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- Branca, Rui M. M. (author)
- Karolinska Institutet
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- Danielsson, Jens (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
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- Xu, Mingming (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
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- Chandler, Shane A. (author)
- Univ Oxford, Dept Chem, Oxford OX1 3QZ, England.
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- Österlund, Nicklas (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
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- Ilag, Leopold L. (author)
- Stockholms universitet,Institutionen för material- och miljökemi (MMK),Stockholm Univ, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
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- Leppert, Axel (author)
- Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden.
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- Costeira-Paulo, Joana (author)
- Uppsala Univ, Dept Chem BMC, S-75123 Uppsala, Sweden.
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- Lang, Lisa (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Univ Oxford, Dept Chem, Oxford OX1 3QZ, England.
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- Teilum, Kaare (author)
- Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 Copenhagen, Denmark.
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- Laganowsky, Arthur (author)
- Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
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Benesch, Justin L. P. (author)
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- Oliveberg, Mikael (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
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- Robinson, Carol V. (author)
- Univ Oxford, Dept Chem, Oxford OX1 3QZ, England.
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- Marklund, Erik, Teknologie doktor, 1979- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Biokemi
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- Allison, Timothy M. (author)
- Univ Canterbury, Biomol Interact Ctr, Sch Phys & Chem Sci, Christchurch 8140, New Zealand.
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- Winther, Jakob R. (author)
- Univ Copenhagen, Linderstrom Lang Ctr Prot Sci, Dept Biol, DK-2200 Copenhagen, Denmark.
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- Landreh, Michael (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17165 Stockholm, Sweden.
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Karolinska Institutet Univ Oxford, Dept Chem, Oxford OX1 3QZ, England (creator_code:org_t)
- 2021-11-29
- 2021
- English.
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In: JACS Au. - : American Chemical Society (ACS). - 2691-3704. ; 1:12, s. 2385-2393
- Related links:
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Abstract
Subject headings
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- In solution, the charge of a protein is intricately linked to its stability, but electrospray ionization distorts this connection, potentially limiting the ability of native mass spectrometry to inform about protein structure and dynamics. How the behavior of intact proteins in the gas phase depends on the presence and distribution of ionizable surface residues has been difficult to answer because multiple chargeable sites are present in virtually all proteins. Turning to protein engineering, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, while coexisting conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. In fact, moving a single ionizable group can dramatically alter the gas-phase conformation of a protein ion. We conclude that although the sum of the charges is governed solely by Coulombic terms, their locations affect the stability of the protein in the gas phase.
Subject headings
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Keyword
- protein folding
- gas-phase conformations
- ion mobility mass spectrometry
Publication and Content Type
- ref (subject category)
- art (subject category)
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JACS Au
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- By the author/editor
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Abramsson, Mia L ...
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Sahin, Cagla
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Hopper, Jonathan ...
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Branca, Rui M. M ...
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Danielsson, Jens
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Xu, Mingming
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show more...
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Chandler, Shane ...
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Österlund, Nickl ...
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Ilag, Leopold L.
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Leppert, Axel
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Costeira-Paulo, ...
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Lang, Lisa
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Teilum, Kaare
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Laganowsky, Arth ...
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Benesch, Justin ...
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Oliveberg, Mikae ...
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Robinson, Carol ...
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Marklund, Erik, ...
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Allison, Timothy ...
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Winther, Jakob R ...
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Landreh, Michael
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Chemical Science ...
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and Physical Chemist ...
- Articles in the publication
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JACS Au
- By the university
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Stockholm University
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Uppsala University
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Karolinska Institutet