Two‐Dimensional Detergent Expansion Strategy for Membrane Protein Studies. Issue 44 (15th June 2022)

• Record Type: Journal Article
• Authors: Zhao, Fei; Zhu, Zhihao; Xie, Linshan; Luo, Feng; Wang, Huixia; Qiu, Yanli; Luo, Weiling; Zhou, Fang; Xue, Dongxiang; Zhang, Zhihui; Hua, Tian; Wu, Dong; Liu, Zhi‐Jie; Le, Zhiping; Tao, Houchao
• Is Part Of: Chemistry. Volume 28:Issue 44(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-15
• Subjects: detergent -- diversity -- EM -- membrane protein -- NMR; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202201388
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Detergents are the most frequently applied reagents in membrane protein (MP) studies. The limited diversity of one‐head‐one‐tailed traditional detergents, however, is far from sufficient for structurally distinct MPs. Expansion of detergent repertoire has a continuous momentum. In line with the speculation that detergent pre‐assembly exerts superiority, herein we report for the first time cross‐conjugation of two series of monomeric detergents for constructing a two‐dimensional library of dimeric detergents. Optimum detergents stood out with unique preferences in the systematic evaluation of individual MPs. Furthermore, unprecedented hybrid detergents 14M8G and 14M9G enabled high‐quality EM study of transporter MsbA and NMR study of G protein‐coupled receptor A2A AR, respectively. Given the abundance of cross‐coupling chemistries, comprehensive diversity could be readily covered that would facilitate the finding of new detergents for the manipulation of thorny MPs and innovation of the functional and structural study in future. Abstract : T‐PADs for membrane proteins : A library of 1, 2, 3‐triazole preassembled detergents (T‐PADs) was constructed two‐dimensionally by click chemistry, exhibiting high diversity with systematic tuning of properties for accommodating distinct membrane proteins. High throughput screening of this detergent library was carried out to explore best matches between detergents and membrane proteins. Among them, structurally unique and unprecedented detergents 14M8G and 14M9G were identified for the EM and NMR study of individual membrane proteins, respectively.