An Engineered Lithocholate‐Based Facial Amphiphile Stabilizes Membrane Proteins: Assessing the Impact of Detergent Customizability on Protein Stability. Issue 39 (13th June 2018)

• Record Type: Journal Article
• Authors: Das, Manabendra; Du, Yang; Mortensen, Jonas S.; Bae, Hyoung Eun; Byrne, Bernadette; Loland, Claus J.; Kobilka, Brian K.; Chae, Pil Seok
• Is Part Of: Chemistry. Volume 24:Issue 39(2018)
• Page Start: 9860
• Page End: 9868
• Publication Date: 2018-06-13
• Subjects: amphiphiles -- membrane proteins -- micelles -- protein stabilization -- protein structures; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201801141
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Amphiphiles are critical tools for the structural and functional study of membrane proteins. Membrane proteins encapsulated by conventional head‐to‐tail detergents tend to undergo structural degradation, necessitating the development of structurally novel agents with improved efficacy. In recent years, facial amphiphiles have yielded encouraging results in terms of membrane protein stability. Herein, we report a new facial detergent (i.e., LFA‐C4) that confers greater stability to tested membrane proteins than the bola form analogue. Owing to the increased facial property and the adaptability of the detergent micelles in complex with different membrane proteins, LFA‐C4 yields increased stability compared to n ‐dodecyl‐β‐d ‐maltoside (DDM). Thus, this study not only describes a novel maltoside detergent with enhanced protein‐stabilizing properties, but also shows that the customizable nature of a detergent plays an important role in the stabilization of membrane proteins. Owing to both synthetic convenience and enhanced stabilization efficacy for a range of membrane proteins, the new agent has major potential in membrane protein research. Abstract : Amp it up ! A comparative study of facial versus bola amphiphiles reveals that LFA‐C4, a facial amphiphile confers greater stability to target membrane proteins than the bola form analogue and n ‐dodecyl‐β‐d ‐maltoside. This result indicates the importance of detergent customizability for membrane protein stability.