Abstract
This perspective describes advances in determining membrane protein structures in lipid bilayers using small-angle neutron scattering (SANS). Differentially labeled detergents with a homogeneous scattering length density facilitate contrast matching of detergent micelles; this has previously been used successfully to obtain the structures of membrane proteins. However, detergent micelles do not mimic the lipid bilayer environment of the cell membrane in vivo. Deuterated vesicles can be used to obtain the radius of gyration of membrane proteins, but protein-protein interference effects within the vesicles severely limits this method such that the protein structure cannot be modeled. We show herein that different membrane protein conformations can be distinguished within the lipid bilayer of the bicontinuous cubic phase using contrast-matching. Time-resolved studies performed using SANS illustrate the complex phase behavior in lyotropic liquid crystalline systems and emphasize the importance of this development. We believe that studying membrane protein structures and phase behavior in contrast-matched lipid bilayers will advance both biological and pharmaceutical applications of membrane-associated proteins, biosensors and food science.
Highlights
Integral and peripheral membrane proteins play an important role in signal transduction, solute transport, energy conversion and charge separation in eukaryotic and prokaryotic cells (Gaur and Natekar, 2010)
We have described current progress on the use of detergent micelles and vesicles to determine membrane protein structures
Neither of these environments have proved wholly successful in determining membrane protein conformations in a lipid bilayer environment
Summary
Integral and peripheral membrane proteins play an important role in signal transduction, solute transport, energy conversion and charge separation in eukaryotic and prokaryotic cells (Gaur and Natekar, 2010). The effects for hydrogens which take part in hydrogen bonding, e.g., water (Takahashi and Jojiki, 2017) are more complex (Bryant et al, 2019) but may account for small shifts in the phase boundaries We describe how this has been used to study proteins in detergent micelles and vesicles and show that this has been successfully applied to study peptide structures in contrastmatched lipid cubic phases. The cubic phase formed by the branched chain lipid phytanoyl monoethanolamine (PE) showed Bragg peaks at low peptide concentrations, but limited WALP21 and WALPS53 encapsulation at high concentrations (van ’t Hag et al, 2016a,b) This can be explained by the significantly higher lateral bilayer pressure in the case of PE bilayers and illustrates the importance of the physicochemical properties of the membrane. This was the first time in meso crystallization was studied from the protein-eye perspective as previous studies using SAXS and SANS without contrast-matching focused, by necessity, on the lipid phase (Efremov et al, 2005; van ’t Hag et al, 2016c; Zabara et al, 2017)
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