Transition‐Linker Containing Detergents for Membrane Protein Studies

Abstract

It is a pressing need, but still challenging to explore the structure and function of membrane proteins (MPs). One of the main obstacles is the limited availability of matched detergents for the handling of specific MPs. We describe herein the design of new detergents by incorporation of a transition linker between the hydrophilic head and the hydrophobic tail. This design allows a gradual change of hydrophobicity between the outside and inside of micelles, in contrast to the abrupt switch in conventional detergents. Notably, many of these detergents assembled into micelles in while retaining low critical micelle concentrations. Meanwhile, thermal stabilizing evaluation identified superior detergents for representative MPs, including G protein‐coupled receptors and a transporter protein. Among them, further improved the NMR study of MPs. We anticipate these that results will encourage future detergent expansion through new remodeling on the traditional detergent scaffold.

Melamine-cored glucosides for membrane protein solubilization and stabilization: importance of water-mediated intermolecular hydrogen bonding in detergent performance

“…This property is also considered benecial for membrane protein structural study via X-ray crystallography, cryo-EM and NMR spectroscopy. 42,43 Interestingly, the sizes of the micelles formed by the MGs only slightly varied with increasing detergent alkyl chain length. The R h of detergent micelles increases by only 0.1 nm with every additional methylene unit to the alkyl chain, smaller than in other classes of amphiphiles.…”