Quantification of Membrane Protein-Detergent Complex Interactions

Aaron J. Wolfe, Wei Si, Zhengqi Zhang, Adam R. Blanden, Yi Ching Hsueh, Jack F. Gugel, Bach Pham, Min Chen, Stewart N. Loh, Sharon Rozovsky, Aleksei Aksimentiev, Liviu Movileanu

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

Although fundamentally significant in structural, chemical, and membrane biology, the interfacial protein-detergent complex (PDC) interactions have been modestly examined because of the complicated behavior of both detergents and membrane proteins in aqueous phase. Membrane proteins are prone to unproductive aggregation resulting from poor detergent solvation, but the participating forces in this phenomenon remain ambiguous. Here, we show that using rational membrane protein design, targeted chemical modification, and steady-state fluorescence polarization spectroscopy, the detergent desolvation of membrane proteins can be quantitatively evaluated. We demonstrate that depleting the detergent in the sample well produced a two-state transition of membrane proteins between a fully detergent-solvated state and a detergent-desolvated state, the nature of which depended on the interfacial PDC interactions. Using a panel of six membrane proteins of varying hydrophobic topography, structural fingerprint, and charge distribution on the solvent-accessible surface, we provide direct experimental evidence for the contributions of the electrostatic and hydrophobic interactions to the protein solvation properties. Moreover, all-atom molecular dynamics simulations report the major contribution of the hydrophobic forces exerted at the PDC interface. This semiquantitative approach might be extended in the future to include studies of the interfacial PDC interactions of other challenging membrane protein systems of unknown structure. This would have practical importance in protein extraction, solubilization, stabilization, and crystallization.

LanguageEnglish (US)
Pages10228-10241
Number of pages14
JournalJournal of Physical Chemistry B
Volume121
Issue number44
DOIs
StatePublished - Nov 9 2017

Fingerprint

detergents
Detergents
Membrane Proteins
membranes
proteins
Proteins
Membranes
interactions
Solvation
solvation
Charge distribution
Chemical modification
Crystallization
Topography
Molecular dynamics
Electrostatics
Agglomeration
Stabilization
biology
Fluorescence

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Wolfe, A. J., Si, W., Zhang, Z., Blanden, A. R., Hsueh, Y. C., Gugel, J. F., ... Movileanu, L. (2017). Quantification of Membrane Protein-Detergent Complex Interactions. Journal of Physical Chemistry B, 121(44), 10228-10241. https://doi.org/10.1021/acs.jpcb.7b08045

Quantification of Membrane Protein-Detergent Complex Interactions. / Wolfe, Aaron J.; Si, Wei; Zhang, Zhengqi; Blanden, Adam R.; Hsueh, Yi Ching; Gugel, Jack F.; Pham, Bach; Chen, Min; Loh, Stewart N.; Rozovsky, Sharon; Aksimentiev, Aleksei; Movileanu, Liviu.

In: Journal of Physical Chemistry B, Vol. 121, No. 44, 09.11.2017, p. 10228-10241.

Research output: Contribution to journalArticle

Wolfe, AJ, Si, W, Zhang, Z, Blanden, AR, Hsueh, YC, Gugel, JF, Pham, B, Chen, M, Loh, SN, Rozovsky, S, Aksimentiev, A & Movileanu, L 2017, 'Quantification of Membrane Protein-Detergent Complex Interactions' Journal of Physical Chemistry B, vol. 121, no. 44, pp. 10228-10241. https://doi.org/10.1021/acs.jpcb.7b08045
Wolfe AJ, Si W, Zhang Z, Blanden AR, Hsueh YC, Gugel JF et al. Quantification of Membrane Protein-Detergent Complex Interactions. Journal of Physical Chemistry B. 2017 Nov 9;121(44):10228-10241. https://doi.org/10.1021/acs.jpcb.7b08045
Wolfe, Aaron J. ; Si, Wei ; Zhang, Zhengqi ; Blanden, Adam R. ; Hsueh, Yi Ching ; Gugel, Jack F. ; Pham, Bach ; Chen, Min ; Loh, Stewart N. ; Rozovsky, Sharon ; Aksimentiev, Aleksei ; Movileanu, Liviu. / Quantification of Membrane Protein-Detergent Complex Interactions. In: Journal of Physical Chemistry B. 2017 ; Vol. 121, No. 44. pp. 10228-10241.
@article{0dafe4d0bcbd4afb994618534e68c293,
title = "Quantification of Membrane Protein-Detergent Complex Interactions",
abstract = "Although fundamentally significant in structural, chemical, and membrane biology, the interfacial protein-detergent complex (PDC) interactions have been modestly examined because of the complicated behavior of both detergents and membrane proteins in aqueous phase. Membrane proteins are prone to unproductive aggregation resulting from poor detergent solvation, but the participating forces in this phenomenon remain ambiguous. Here, we show that using rational membrane protein design, targeted chemical modification, and steady-state fluorescence polarization spectroscopy, the detergent desolvation of membrane proteins can be quantitatively evaluated. We demonstrate that depleting the detergent in the sample well produced a two-state transition of membrane proteins between a fully detergent-solvated state and a detergent-desolvated state, the nature of which depended on the interfacial PDC interactions. Using a panel of six membrane proteins of varying hydrophobic topography, structural fingerprint, and charge distribution on the solvent-accessible surface, we provide direct experimental evidence for the contributions of the electrostatic and hydrophobic interactions to the protein solvation properties. Moreover, all-atom molecular dynamics simulations report the major contribution of the hydrophobic forces exerted at the PDC interface. This semiquantitative approach might be extended in the future to include studies of the interfacial PDC interactions of other challenging membrane protein systems of unknown structure. This would have practical importance in protein extraction, solubilization, stabilization, and crystallization.",
author = "Wolfe, {Aaron J.} and Wei Si and Zhengqi Zhang and Blanden, {Adam R.} and Hsueh, {Yi Ching} and Gugel, {Jack F.} and Bach Pham and Min Chen and Loh, {Stewart N.} and Sharon Rozovsky and Aleksei Aksimentiev and Liviu Movileanu",
year = "2017",
month = "11",
day = "9",
doi = "10.1021/acs.jpcb.7b08045",
language = "English (US)",
volume = "121",
pages = "10228--10241",
journal = "Journal of Physical Chemistry B",
issn = "1520-6106",
number = "44",

}

TY - JOUR

T1 - Quantification of Membrane Protein-Detergent Complex Interactions

AU - Wolfe, Aaron J.

AU - Si, Wei

AU - Zhang, Zhengqi

AU - Blanden, Adam R.

AU - Hsueh, Yi Ching

AU - Gugel, Jack F.

AU - Pham, Bach

AU - Chen, Min

AU - Loh, Stewart N.

AU - Rozovsky, Sharon

AU - Aksimentiev, Aleksei

AU - Movileanu, Liviu

PY - 2017/11/9

Y1 - 2017/11/9

N2 - Although fundamentally significant in structural, chemical, and membrane biology, the interfacial protein-detergent complex (PDC) interactions have been modestly examined because of the complicated behavior of both detergents and membrane proteins in aqueous phase. Membrane proteins are prone to unproductive aggregation resulting from poor detergent solvation, but the participating forces in this phenomenon remain ambiguous. Here, we show that using rational membrane protein design, targeted chemical modification, and steady-state fluorescence polarization spectroscopy, the detergent desolvation of membrane proteins can be quantitatively evaluated. We demonstrate that depleting the detergent in the sample well produced a two-state transition of membrane proteins between a fully detergent-solvated state and a detergent-desolvated state, the nature of which depended on the interfacial PDC interactions. Using a panel of six membrane proteins of varying hydrophobic topography, structural fingerprint, and charge distribution on the solvent-accessible surface, we provide direct experimental evidence for the contributions of the electrostatic and hydrophobic interactions to the protein solvation properties. Moreover, all-atom molecular dynamics simulations report the major contribution of the hydrophobic forces exerted at the PDC interface. This semiquantitative approach might be extended in the future to include studies of the interfacial PDC interactions of other challenging membrane protein systems of unknown structure. This would have practical importance in protein extraction, solubilization, stabilization, and crystallization.

AB - Although fundamentally significant in structural, chemical, and membrane biology, the interfacial protein-detergent complex (PDC) interactions have been modestly examined because of the complicated behavior of both detergents and membrane proteins in aqueous phase. Membrane proteins are prone to unproductive aggregation resulting from poor detergent solvation, but the participating forces in this phenomenon remain ambiguous. Here, we show that using rational membrane protein design, targeted chemical modification, and steady-state fluorescence polarization spectroscopy, the detergent desolvation of membrane proteins can be quantitatively evaluated. We demonstrate that depleting the detergent in the sample well produced a two-state transition of membrane proteins between a fully detergent-solvated state and a detergent-desolvated state, the nature of which depended on the interfacial PDC interactions. Using a panel of six membrane proteins of varying hydrophobic topography, structural fingerprint, and charge distribution on the solvent-accessible surface, we provide direct experimental evidence for the contributions of the electrostatic and hydrophobic interactions to the protein solvation properties. Moreover, all-atom molecular dynamics simulations report the major contribution of the hydrophobic forces exerted at the PDC interface. This semiquantitative approach might be extended in the future to include studies of the interfacial PDC interactions of other challenging membrane protein systems of unknown structure. This would have practical importance in protein extraction, solubilization, stabilization, and crystallization.

UR - http://www.scopus.com/inward/record.url?scp=85033596888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033596888&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.7b08045

DO - 10.1021/acs.jpcb.7b08045

M3 - Article

VL - 121

SP - 10228

EP - 10241

JO - Journal of Physical Chemistry B

T2 - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 44

ER -