TY - JOUR AB - Amphipathic agents are widely used in various fields including biomedical sciences. Micelle-forming detergents are particularly useful for in vitro membrane-protein characterization. As many conventional detergents are limited in their ability to stabilize membrane proteins, it is necessary to develop novel detergents to facilitate membrane-protein research. In the current study, we developed novel trimaltoside detergents with an alkyl pendant-bearing terphenyl unit as a hydrophobic group, designated terphenyl-cored maltosides (TPMs). We found that the geometry of the detergent hydrophobic group substantially impacts detergent self-assembly behavior, as well as detergent efficacy for membrane-protein stabilization. TPM-Vs, with a bent terphenyl group, were superior to the linear counterparts (TPM-Ls) at stabilizing multiple membrane proteins. The favorable protein stabilization efficacy of these bent TPMs is likely associated with a binding mode with membrane proteins distinct from conventional detergents and facial amphiphiles. When compared to n-dodecyl-β-d-maltoside (DDM), most TPMs were superior or comparable to this gold standard detergent at stabilizing membrane proteins. Notably, TPM-L3 was particularly effective at stabilizing the human β2 adrenergic receptor (β2 AR), a G-protein coupled receptor, and its complex with Gs protein. Thus, the current study not only provides novel detergent tools that are useful for membrane-protein study, but also suggests a critical role for detergent hydrophobic group geometry in governing detergent efficacy. AU - Ehsan,M AU - Du,Y AU - Mortensen,JS AU - Hariharan,P AU - Qu,Q AU - Ghani,L AU - Das,M AU - Grethen,A AU - Byrne,B AU - Skiniotis,G AU - Keller,S AU - Loland,CJ AU - Guan,L AU - Kobilka,BK AU - Chae,PS DO - 10.1002/chem.201902468 EP - 11554 PY - 2019/// SN - 0947-6539 SP - 11545 TI - Self-assembly behavior and application of terphenyl-cored trimaltosides for membrane-protein studies: impact of detergent hydrophobic group geometry on protein stability T2 - Chemistry - A European Journal UR - http://dx.doi.org/10.1002/chem.201902468 UR - https://www.ncbi.nlm.nih.gov/pubmed/31243822 UR - https://onlinelibrary.wiley.com/doi/full/10.1002/chem.201902468 UR - http://hdl.handle.net/10044/1/72914 VL - 25 ER -