| Affiliation: | 1. Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, Ansan, 155-88 South Korea;2. School of Computational Sciences, Korea Institute for Advanced Study, Seoul, 024-55 South Korea;3. Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305 USA;4. Department of Neuroscience, University of Copenhagen, Copenhagen, 2200 Denmark;5. Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430 USA;6. Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305 USA Current address: School of Life and Health Sciences, Chinese University of Hong Kong, 2001 Longxiang Ave, Shenzhen, Guangdong, 518172 China;7. Department of Life Sciences, Imperial College London, London, SW7 2AZ UK;8. Department of Biological Sciences, Chemistry, and Bioengineering, Lehigh University, Bethlehem, PA 18015 USA |
| Abstract: | Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools are suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM−Hs) and 1,2-ethylenediamine (TZM−Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM−Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM−Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM−Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential in rational detergent design and membrane protein applications. |
