Foldable detergents for membrane protein study: Importance of detergent core flexibility in protein stabilization
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Foldable detergents for membrane protein study : Importance of detergent core flexibility in protein stabilization. / Ghani, Lubna; Kim, Seonghoon; Wang, Haoqing; Lee, Hyun Sung; Mortensen, Jonas S; Katsube, Satoshi; Du, Yang; Sadaf, Aiman; Byrne, Bernadette; Guan, Lan; Loland, Claus J; Kobilka, Brian K; Im, Wonpil; Chae, Pil Seok; Ahmed, Waqar.
In: Chemistry: A European Journal, Vol. 28, No. 21, e202200116, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Foldable detergents for membrane protein study
T2 - Importance of detergent core flexibility in protein stabilization
AU - Ghani, Lubna
AU - Kim, Seonghoon
AU - Wang, Haoqing
AU - Lee, Hyun Sung
AU - Mortensen, Jonas S
AU - Katsube, Satoshi
AU - Du, Yang
AU - Sadaf, Aiman
AU - Byrne, Bernadette
AU - Guan, Lan
AU - Loland, Claus J
AU - Kobilka, Brian K
AU - Im, Wonpil
AU - Chae, Pil Seok
AU - Ahmed, Waqar
N1 - © 2022 Wiley-VCH GmbH.
PY - 2022
Y1 - 2022
N2 - Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools is suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM-Hs) and 1,2-ethylenediamine (TZM-Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM-Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM-Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM-Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential use for rational detergent design and membrane protein applications.
AB - Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools is suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM-Hs) and 1,2-ethylenediamine (TZM-Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM-Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM-Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM-Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential use for rational detergent design and membrane protein applications.
U2 - 10.1002/chem.202200116
DO - 10.1002/chem.202200116
M3 - Journal article
C2 - 35238091
VL - 28
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 21
M1 - e202200116
ER -
ID: 299388785