Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies

TY - JOUR

T1 - Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies

AU - Ehsan, Muhammad

AU - Du, Yang

AU - Scull, Nicola J

AU - Tikhonova, Elena

AU - Tarrasch, Jeffrey

AU - Mortensen, Jonas S

AU - Loland, Claus J

AU - Skiniotis, Georgios

AU - Guan, Lan

AU - Byrne, Bernadette

AU - Kobilka, Brian K

AU - Chae, Pil Seok

PY - 2016/3/23

Y1 - 2016/3/23

N2 - Detergents are essential tools for membrane protein manipulation. Micelles formed by detergent molecules have the ability to encapsulate the hydrophobic domains of membrane proteins. The resulting protein-detergent complexes (PDCs) are compatible with the polar environments of aqueous media, making structural and functional analysis feasible. Although a number of novel agents have been developed to overcome the limitations of conventional detergents, most have traditional head groups such as glucoside or maltoside. In this study, we introduce a class of amphiphiles, the PSA/Es with a novel highly branched pentasaccharide hydrophilic group. The PSA/Es conferred markedly increased stability to a diverse range of membrane proteins compared to conventional detergents, indicating a positive role for the new hydrophilic group in maintaining the native protein integrity. In addition, PDCs formed by PSA/Es were smaller and more suitable for electron microscopic analysis than those formed by DDM, indicating that the new agents have significant potential for the structure-function studies of membrane proteins.

AB - Detergents are essential tools for membrane protein manipulation. Micelles formed by detergent molecules have the ability to encapsulate the hydrophobic domains of membrane proteins. The resulting protein-detergent complexes (PDCs) are compatible with the polar environments of aqueous media, making structural and functional analysis feasible. Although a number of novel agents have been developed to overcome the limitations of conventional detergents, most have traditional head groups such as glucoside or maltoside. In this study, we introduce a class of amphiphiles, the PSA/Es with a novel highly branched pentasaccharide hydrophilic group. The PSA/Es conferred markedly increased stability to a diverse range of membrane proteins compared to conventional detergents, indicating a positive role for the new hydrophilic group in maintaining the native protein integrity. In addition, PDCs formed by PSA/Es were smaller and more suitable for electron microscopic analysis than those formed by DDM, indicating that the new agents have significant potential for the structure-function studies of membrane proteins.

U2 - 10.1021/jacs.5b13233

DO - 10.1021/jacs.5b13233

M3 - Journal article

C2 - 26966956

SN - 0002-7863

VL - 138

SP - 3789

EP - 3796

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 11

ER -