Abstract
Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) at the neutron contrast match point of detergent molecules allows observing the signal from membrane proteins unobstructed by contributions from the detergent. However, we show that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal interferes with interpreting structural data of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. We present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell and allows the micelle scattering to be fully contrast-matched to unambiguously resolve membrane protein structure using solution SANS.
Original language | English |
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Pages (from-to) | 5041-5046 |
Number of pages | 6 |
Journal | Journal of Physical Chemistry Letters |
Volume | 8 |
Issue number | 20 |
DOIs | |
State | Published - Oct 19 2017 |
Funding
Neutron scattering studies at the CG-3 Bio-SANS instrument at the High-Flux Isotope Reactor of Oak Ridge National Laboratory were sponsored by the Office of Biological and Environmental Research and by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. This work benefited from the use of the SasView application, originally developed under NSF Award DMR-0520547. SasView contains code developed with funding from the European Union’s Horizon 2020 Research and Innovation Programme under the SINE2020 project, Grant Agreement No 654000. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).