Disulfide‐Containing Detergents (DCDs) for the Structural Biology of Membrane Proteins

• Published in: Chemistry : a European journal 2019-09, Vol.25 (50), p.11635-11640
• Main Authors: Xue, Dongxiang, Xu, Tiandan, Wang, Huixia, Wu, Meng, Yuan, Ya, Wang, Wei, Tan, Qiwen, Zhao, Fei, Zhou, Fang, Hu, Tao, Jiang, Zhongxing, Liu, Zhi‐Jie, Zhao, Suwen, Liu, Dongsheng, Wüthrich, Kurt, Tao, Houchao
• Format: Article
• Language: English
• Subjects: Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Biology; Chemistry; Detergents; Detergents - chemistry; disulfides; Disulfides - chemistry; E coli; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Humans; Hydrolases - chemistry; Hydrolases - metabolism; Hydrophobicity; Membrane proteins; micelle size; Micelles; Molecular chains; NMR; NMR spectroscopy; Nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; Protein Stability; Proteins; Receptor, Adenosine A2A - chemistry; Receptor, Adenosine A2A - metabolism; Solubilization
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201903190

Disulfide‐containing detergents (DCDs) are introduced, which contain a disulfide bond in the hydrophobic tail. DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins. The use of this new class of detergents in structural biology is illustrated with solution NMR spectra of the human G protein‐coupled receptor A2AAR, which is an α‐helical protein, and the β‐barrel protein OmpX from E. coli. Bending for better: Detergents with a bent disulfide hinge in their hydrophobic tail facilitate efficient membrane protein solubilization and stabilization in small micelles. This new set of detergents can be feasibly used in NMR studies on α‐helical and β‐barrel membrane proteins (see figure).