A 10-year meta-analysis of membrane protein structural biology: Detergents, membrane mimetics, and structure determination techniques

Structure determination of membrane proteins is critical to the molecular understanding of many life processes, yet it has historically been a technically challenging endeavor. This past decade has given rise to a number of technological advancements, techniques, and reagents, which have facilitated membrane protein structural biology, resulting in an ever-growing number of membrane protein structures determined. To collate these advances, we have mined available literature to analyze the purification and structure determination specifics for all uniquely solved membrane protein structures from 2010 to 2019. Our analyses demonstrate the strong impact of single-particle cryo-electron microscopy on the field and illustrate how this technique has affected detergent and membrane mimetic usage. Furthermore, we detail how different structure determination methods, taxonomic domains and protein classes have unique detergent/membrane mimetic profiles, highlighting the importance of tailoring their selection. Our analyses provide a quantitative overview of where the field of membrane protein structural biology stands and how it has developed over time. We anticipate that these will serve as a useful tool to streamline future membrane protein structure determination by guiding the choice of detergent/membrane mimetic. [Display omitted] •Tailored detergent selection is crucial for membrane protein structural biology.•Generation of a detergent and membrane mimetic dataset covering 2010–2019.•Protein type and structure determination method impact detergent choice.•Nanodiscs and amphipols have increased in popularity over the last decade.•Cryo-EM has significantly impacted membrane protein structural biology.