Studying system biology at the atomic level

Outlet: Nature Methods
Published: January 6, 2021

A ‘Build and Retrieve’ methodology to simultaneously solve cryo-EM structures of membrane proteins


Authors: Edward Yu, professor of pharmacology at CWRU School of Medicine and researchers from the University of Oxford, Oxford, UK

Photo of Edward Yu

Single-particle cryo-electron microscopy (cryo-EM) has become a powerful technique in the field of structural biology. However, the inability to reliably produce pure, homogeneous membrane protein samples significantly hampers the progress of their structural determination. 

Edward Yu and a team of researchers from the University of Oxford developed a bottom-up iterative method, Build and Retrieve (BaR), that enables the identification and determination of cryo-EM structures of a variety of inner- and outer-membrane proteins, including membrane protein complexes of different sizes and dimensions, from a native, heterogeneous, impure protein sample. 

Prior to cryo-EM technology, structural determination requires homogeneous and pure samples. Sample heterogeneity often hampers the progress of drug design and development, especially with regard to the drugs that target membrane proteins and complexes. The findings demonstrate that it is possible to solve high-resolution structures of a number of relatively small unidentified membrane proteins within a single, heterogeneous sample. These results highlight the potential of cryo-EM for systems structural proteomics.