An Engineered Lithocholate-Based Facial Amphiphile Stabilizes Membrane Proteins: Assessing the Impact of Detergent Customizability on Protein Stability

TY - JOUR

T1 - An Engineered Lithocholate-Based Facial Amphiphile Stabilizes Membrane Proteins

T2 - Assessing the Impact of Detergent Customizability on Protein Stability

AU - Das, Manabendra

AU - Du, Yang

AU - Mortensen, Jonas S.

AU - Bae, Hyoung Eun

AU - Byrne, Bernadette

AU - Loland, Claus J.

AU - Kobilka, Brian K.

AU - Chae, Pil Seok

PY - 2018/7/11

Y1 - 2018/7/11

N2 - 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.

AB - 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.

KW - amphiphiles

KW - membrane proteins

KW - micelles

KW - protein stabilization

KW - protein structures

KW - Membrane Proteins/chemistry

KW - Micelles

KW - Hydrophobic and Hydrophilic Interactions

KW - Protein Stability

KW - Lithocholic Acid

KW - Detergents/chemistry

U2 - 10.1002/chem.201801141

DO - 10.1002/chem.201801141

M3 - Journal article

C2 - 29741269

AN - SCOPUS:85049774129

SN - 0947-6539

VL - 24

SP - 9860

EP - 9868

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 39

ER -