Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

Kyung Ho Cho; Parameswaran Hariharan; Jonas S. Mortensen; Yang Du; Anne K. Nielsen; Bernadette Byrne; Brian K. Kobilka; Claus J. Loland; Lan Guan; Pil Seok Chae

doi:10.1002/cbic.201600429

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

Kyung Ho Cho, Parameswaran Hariharan, Jonas S. Mortensen, Yang Du, Anne K. Nielsen, Bernadette Byrne, Brian K. Kobilka, Claus J. Loland, Lan Guan, Pil Seok Chae

Neuropharm and Genetics

10 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	ChemBioChem
Vol/bind	17
Udgave nummer	24
Sider (fra-til)	2334–2339
ISSN	1439-4227
DOI	https://doi.org/10.1002/cbic.201600429
Status	Udgivet - 14 dec. 2016

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10.1002/cbic.201600429

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@article{3c27979da00144b3ab9beaa09bb9ee0a,

title = "Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length",

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.",

author = "Cho, {Kyung Ho} and Parameswaran Hariharan and Mortensen, {Jonas S.} and Yang Du and Nielsen, {Anne K.} and Bernadette Byrne and Kobilka, {Brian K.} and Loland, {Claus J.} and Lan Guan and Chae, {Pil Seok}",

year = "2016",

month = dec,

day = "14",

doi = "10.1002/cbic.201600429",

language = "English",

volume = "17",

pages = "2334–2339",

journal = "ChemBioChem",

issn = "1439-4227",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "24",

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TY - JOUR

T1 - Isomeric Detergent Comparison for Membrane Protein Stability

T2 - Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

AU - Cho, Kyung Ho

AU - Hariharan, Parameswaran

AU - Mortensen, Jonas S.

AU - Du, Yang

AU - Nielsen, Anne K.

AU - Byrne, Bernadette

AU - Kobilka, Brian K.

AU - Loland, Claus J.

AU - Guan, Lan

AU - Chae, Pil Seok

PY - 2016/12/14

Y1 - 2016/12/14

N2 - 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.

AB - 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.

U2 - 10.1002/cbic.201600429

DO - 10.1002/cbic.201600429

M3 - Journal article

C2 - 27981750

SN - 1439-4227

VL - 17

SP - 2334

EP - 2339

JO - ChemBioChem

JF - ChemBioChem

IS - 24

ER -

Isomeric Detergent Comparison for Membrane Protein Stability: Importance of Inter-Alkyl-Chain Distance and Alkyl Chain Length

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