NDT‐C11 as a Viable Novel Detergent for Single Particle Cryo‐EM

Abstract

Single particle cryo electron microscopy (cryo‐EM) is now the major method for the determination of integral membrane protein structure. For the success of a given project the type of membrane mimetic used for extraction from the native cell membrane, purification to homogeneity and finally cryo‐grid vitrification is crucial. Although small molecule amphiphiles – detergents – are the most widely used membrane mimetic, specific tailoring of detergent structure for single particle cryo‐EM is rare and the demand for effective detergents not satisfied. Here, we compare the popular detergent lauryl maltose‐neopentyl glycol (LMNG) with the novel detergent neopentyl glycol‐derived triglucoside‐C11 (NDT‐C11) in its behavior as free detergent and when bound to two types of multisubunit membrane protein complexes — cyanobacterial photosystem I (PSI) and mammalian F‐ATP synthase. We conclude that NDT‐C11 has high potential to become a very useful detergent for single particle cryo‐EM of integral membrane proteins.