This process is labour intensive, unreliable, and means further separation steps are needed to isolate the proteins before they can be used. In 2015, a new approach was developed by another US-based research group that involves encircling a membrane protein with a naturally-occurring apolipoprotein AI.1 This protein is amphipathic \u2013 it has a lipophilic interior that interacts with hydrophobic residues on the membrane protein\u2019s surface, and a hydrophilic exterior that makes the whole complex soluble in aqueous solution. However, the interaction between apolipoprotein AI and proteins is non-specific.<\/p>\n
Wrappers delight<\/p>\n
Mihaljevi\u0107 and colleagues in the group of David Baker<\/a> \u2013 who shared the 2024 Nobel Prize in chemistry for computational protein design<\/a> \u2013 have now used their deep learning algorithm RF diffusion to custom design protein sheaths called Wraps (water-soluble RF-diffused amphipathic proteins) that are tailored to encapsulate the cell-bound regions of specific target proteins while leaving their functional ends free.2 The amino acid sequence for these Wraps are then genetically encoded and expressed along with the membrane protein in Escherichia coli bacteria. The team has used the approach to capture and analyse a variety of membrane proteins.<\/p>\n The researchers looked at a Mycobacterial porin protein whose structure had previously been solved using traditional methods. \u2018What we are able to do right now is confirm a structure that is unchanged based on the previous structure,\u2019 says Mihaljevi\u0107; \u2018Unfortunately other proteins that we were able to wrap were too small to be able to actually solve the structure.\u2019 As methods such as cryo-electron microscopy improve, the researchers hope it will be possible to ascertain structures of smaller wrapped proteins directly.<\/p>\n The researchers then studied other proteins, including outer-membrane proteins of the Treponema pallidum bacterium, which causes syphilis. The researchers used the AlphaFold protein folding algorithm to predict the shapes of the folded proteins and then designed Wrap sheaths to fit those structures. They found that the resulting sheaths could bind the proteins and stabilise them in solution. The bound proteins showed reactivity towards serum extracted from syphilis-infected rabbits. Mihaljevi\u0107 says the current work is \u2018just a proof of concept,\u2019 but reveals that collaborating laboratories are studying the technology\u2019s potential for monoclonal antibodies and vaccines.<\/p>\n![\"The](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2026\/07\/549963_wc29_06_2026_proteinwrapsinarticle_785389.jpg\")
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