Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter‐Alkyl‐Chain Distance and Alkyl Chain Length. (7th November 2016)

• Record Type: Journal Article
• Authors: Cho, Kyung Ho; Hariharan, Parameswaran; Mortensen, Jonas S.; Du, Yang; Nielsen, Anne K.; Byrne, Bernadette; Kobilka, Brian K.; Loland, Claus J.; Guan, Lan; Chae, Pil Seok
• Is Part Of: Chembiochem. Volume 17:Number 24(2016)
• Page Start: 2334
• Page End: 2339
• Publication Date: 2016-11-07
• Subjects: amphiphiles -- detergents -- membrane proteins -- noncovalent interactions -- protein solubilization -- protein stabilization; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600429
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Membrane proteins encapsulated by detergent micelles are widely used for structural study. Because of their amphipathic property, detergents have the ability to maintain protein solubility and stability in an aqueous medium. However, conventional detergents have serious limitations in their scope and utility, particularly for eukaryotic membrane proteins and membrane protein complexes. Thus, a number of new agents have been devised; some have made significant contributions to membrane protein structural studies. However, few detergent design principles are available. In this study, we prepared meta and ortho isomers of the previously reported para ‐substituted xylene‐linked maltoside amphiphiles (XMAs), along with alkyl chain‐length variation. The isomeric XMAs were assessed with three membrane proteins, and the meta isomer with a C12 alkyl chain was most effective at maintaining solubility/stability of the membrane proteins. We propose that interplay between the hydrophile–lipophile balance (HLB) and alkyl chain length is of central importance for high detergent efficacy. In addition, differences in inter‐alkyl‐chain distance between the isomers influence the ability of the detergents to stabilise membrane proteins. Abstract : Isomeric detergent comparison enabled us to discover new detergent design principles, by synthesising and testing meta and ortho isomers of our previous para ‐substituted xylene‐linked maltoside amphiphiles. Our results will facilitate the design of new detergents with enhanced membrane‐protein stabilisation efficacy.