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, and Liviu Movileanu.
Quantification of membrane protein-detergent complex interactions.
Journal of Physical Chemistry B, 121:10228-10241, 2017.
(PMC: PMC5680101)
WOLF2017-AA
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.
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