Maltose neopentyl glycol-3 (MNG-3) analogues for membrane protein study

TY - JOUR

T1 - Maltose neopentyl glycol-3 (MNG-3) analogues for membrane protein study

AU - Cho, Kyung Ho

AU - Husri, Mohd

AU - Amin, Anowarul

AU - Gotfryd, Kamil

AU - Lee, Ho Jin

AU - Go, Juyeon

AU - Kim, Jin Woong

AU - Loland, Claus J

AU - Guan, Lan

AU - Byrne, Bernadette

AU - Chae, Pil Seok

PY - 2015/5/7

Y1 - 2015/5/7

N2 - Detergents are typically used to both extract membrane proteins (MPs) from the lipid bilayers and maintain them in solution. However, MPs encapsulated in detergent micelles are often prone to denaturation and aggregation. Thus, the development of novel agents with enhanced stabilization characteristics is necessary to advance MP research. Maltose neopentyl glycol-3 (MNG-3) has contributed to >10 crystal structures including G-protein coupled receptors. Here, we prepared MNG-3 analogues and characterised their properties using selected MPs. Most MNGs were superior to a conventional detergent, n-dodecyl-β-d-maltopyranoside (DDM), in terms of membrane protein stabilization efficacy. Interestingly, optimal stabilization was achieved with different MNG-3 analogues depending on the target MP. The origin for such detergent specificity could be explained by a novel concept: compatibility between detergent hydrophobicity and MP tendency to denature and aggregate. This set of MNGs represents viable alternatives to currently available detergents for handling MPs, and can be also used as tools to estimate MP sensitivity to denaturation and aggregation.

AB - Detergents are typically used to both extract membrane proteins (MPs) from the lipid bilayers and maintain them in solution. However, MPs encapsulated in detergent micelles are often prone to denaturation and aggregation. Thus, the development of novel agents with enhanced stabilization characteristics is necessary to advance MP research. Maltose neopentyl glycol-3 (MNG-3) has contributed to >10 crystal structures including G-protein coupled receptors. Here, we prepared MNG-3 analogues and characterised their properties using selected MPs. Most MNGs were superior to a conventional detergent, n-dodecyl-β-d-maltopyranoside (DDM), in terms of membrane protein stabilization efficacy. Interestingly, optimal stabilization was achieved with different MNG-3 analogues depending on the target MP. The origin for such detergent specificity could be explained by a novel concept: compatibility between detergent hydrophobicity and MP tendency to denature and aggregate. This set of MNGs represents viable alternatives to currently available detergents for handling MPs, and can be also used as tools to estimate MP sensitivity to denaturation and aggregation.

U2 - 10.1039/c5an00240k

DO - 10.1039/c5an00240k

M3 - Journal article

C2 - 25813698

SN - 0003-2654

VL - 140

SP - 3157

EP - 3163

JO - The Analyst

JF - The Analyst

IS - 9

ER -