Abstract
A crucial bottleneck in membrane protein structural biology is the difficulty in identifying a detergent that can maintain the stability and functionality of integral membrane proteins (IMPs). Detergents are poor membrane mimics, and their common use in membrane protein crystallography may be one reason for the challenges in obtaining high‐resolution crystal structures of many IMP families. Lipid‐like peptides (LLPs) have detergent‐like properties and have been proposed as alternatives for the solubilization of G protein‐coupled receptors and other membrane proteins. Here, we systematically analyzed the stabilizing effect of LLPs on integral membrane proteins of different families. We found that LLPs could significantly stabilize detergent‐solubilized IMPs in vitro. This stabilizing effect depended on the chemical nature of the LLP and the intrinsic stability of a particular IMP in the detergent. Our results suggest that screening a subset of LLPs is sufficient to stabilize a particular IMP, which can have a substantial impact on the crystallization and quality of the crystal.
Highlights
Membrane proteins represent about one third of the proteins in living organisms[1] and play central roles in all physiological processes
We systematically evaluated the effect of lipidlike peptides on the stability of integral membrane proteins
We designed a series of small, amphiphilic lipid-like peptides possessing detergent-like properties and consisting of a short hydrophobic tail and a hydrophilic head group,[18] and we systematically varied the charges and length of the hydrophobic tail
Summary
Membrane proteins represent about one third of the proteins in living organisms[1] and play central roles in all physiological processes.
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