New Malonate-Derived Tetraglucoside Detergents for Membrane Protein Stability
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New Malonate-Derived Tetraglucoside Detergents for Membrane Protein Stability. / Ehsan, Muhammad; Katsube, Satoshi; Cecchetti, Cristina; Du, Yang; Mortensen, Jonas S.; Wang, Haoqing; Nygaard, Andreas; Ghani, Lubna; Loland, Claus Juul; Kobilka, Brian K.; Byrne, Bernadette; Guan, Lan; Chae, Pil Seok.
In: ACS chemical biology, Vol. 15, No. 6, 2020, p. 1697-1707.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - New Malonate-Derived Tetraglucoside Detergents for Membrane Protein Stability
AU - Ehsan, Muhammad
AU - Katsube, Satoshi
AU - Cecchetti, Cristina
AU - Du, Yang
AU - Mortensen, Jonas S.
AU - Wang, Haoqing
AU - Nygaard, Andreas
AU - Ghani, Lubna
AU - Loland, Claus Juul
AU - Kobilka, Brian K.
AU - Byrne, Bernadette
AU - Guan, Lan
AU - Chae, Pil Seok
PY - 2020
Y1 - 2020
N2 - Membrane proteins are widely studied in detergent micelles, a inembranc-mimetic system formed by amphiphilic compounds. However, classical detergents have serious limitations in their utility, particularly for unstable proteins such as eukaryotic membrane proteins and membrane protein complexes, and thus, there is an unmet need for novel amphiphiles with enhanced ability to stabilize membrane proteins. Here, we developed a new class of malonate-derived detergents with four glucosides, designated malonate-derived tetra-glucosides (MTGs), and compared these new detergents with previously reported octyl glucose neopentyl glycol (OGNG) and n-dodecyl-beta-D-maltoside (DDM). When tested with two G-protein coupled receptors (GPCRs) and three transporters, a couple of MTGs consistently conferred enhanced stability to all tested proteins compared to DDM and OGNG. As a result of favorable behaviors for a range of membrane proteins, these MTGs have substantial potential for membrane protein research. This study additionally provides a new detergent design principle based on the effect of a polar functional group (i.e., ether) on protein stability depending on its position in the detergent scaffold.
AB - Membrane proteins are widely studied in detergent micelles, a inembranc-mimetic system formed by amphiphilic compounds. However, classical detergents have serious limitations in their utility, particularly for unstable proteins such as eukaryotic membrane proteins and membrane protein complexes, and thus, there is an unmet need for novel amphiphiles with enhanced ability to stabilize membrane proteins. Here, we developed a new class of malonate-derived detergents with four glucosides, designated malonate-derived tetra-glucosides (MTGs), and compared these new detergents with previously reported octyl glucose neopentyl glycol (OGNG) and n-dodecyl-beta-D-maltoside (DDM). When tested with two G-protein coupled receptors (GPCRs) and three transporters, a couple of MTGs consistently conferred enhanced stability to all tested proteins compared to DDM and OGNG. As a result of favorable behaviors for a range of membrane proteins, these MTGs have substantial potential for membrane protein research. This study additionally provides a new detergent design principle based on the effect of a polar functional group (i.e., ether) on protein stability depending on its position in the detergent scaffold.
KW - CRYSTAL-STRUCTURE
KW - BETA(2)-ADRENERGIC RECEPTOR
KW - ALLOSTERIC MODULATION
KW - AMPHIPHILES
KW - SOLUBILIZATION
KW - BINDING
KW - STABILIZATION
KW - INSIGHTS
KW - MICELLAR
KW - COMPLEX
U2 - 10.1021/acschembio.0c00316
DO - 10.1021/acschembio.0c00316
M3 - Journal article
C2 - 32501004
VL - 15
SP - 1697
EP - 1707
JO - A C S Chemical Biology
JF - A C S Chemical Biology
SN - 1554-8929
IS - 6
ER -
ID: 246670354