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0Scientists have developed a new class of de novo–designed proteins called WRAPs (water-soluble RFdiffused amphipathic proteins) to solve the long-standing challenge of membrane protein solubilization. These artificial proteins are engineered using deep learning tools like RFdiffusion to "wrap" around the water-repelling regions of membrane proteins, allowing them to remain stable in water without the need for detergents. This method preserves the natural structure and function of the target proteins, facilitating the study of complex molecules involved in signaling, infection, and drug response. Researchers successfully applied this technology to diverse targets, including syphilis antigens and GPCRs, which were previously difficult to produce and analyze. Notably, the study achieved a high-resolution cryo-EM structure of a WRAP-stabilized porin, proving the method's efficacy for structural biology. Ultimately, WRAPs offer a streamlined workflow for vaccine design and drug discovery by enabling the direct expression of soluble membrane proteins in bacteria.
References:
Mihaljević L, Kim D E, Bandawane P D, et al. Membrane protein solubilization and structure determination using de novo–designed proteins[J]. Science, 2026, 393(6806): eadr3817.
