Conformationally
Preorganized Diastereomeric Norbornane-Based
Maltosides for Membrane Protein Study: Implications of Detergent Kink
for Micellar Properties
Posted on 2017-02-20 - 18:20
Detergents
are essential tools for functional and structural studies
of membrane proteins. However, conventional detergents are limited
in their scope and utility, particularly for eukaryotic membrane proteins.
Thus, there are major efforts to develop new amphipathic agents with
enhanced properties. Here, a novel class of diastereomeric agents
with a preorganized conformation, designated norbornane-based maltosides
(NBMs), were prepared and evaluated for their ability to solubilize
and stabilize membrane proteins. Representative NBMs displayed enhanced
behaviors compared to n-dodecyl-β-d-maltoside (DDM) for all membrane proteins tested. Efficacy of the
individual NBMs varied depending on the overall detergent shape and
alkyl chain length. Specifically, NBMs with no kink in the lipophilic
region conferred greater stability to the proteins than NBMs with
a kink. In addition, long alkyl chain NBMs were generally better at
stabilizing membrane proteins than short alkyl chain agents. Furthermore,
use of one well-behaving NBM enabled us to attain a marked stabilization
and clear visualization of a challenging membrane protein complex
using electron microscopy. Thus, this study not only describes novel
maltoside detergents with enhanced protein-stabilizing properties
but also suggests that overall detergent geometry has an important
role in determining membrane protein stability. Notably, this is the
first systematic study on the effect of detergent kinking on micellar
properties and associated membrane protein stability.
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Das, Manabendra; Du, Yang; Ribeiro, Orquidea; Hariharan, Parameswaran; Mortensen, Jonas S.; Patra, Dhabaleswar; et al. (2017). Conformationally
Preorganized Diastereomeric Norbornane-Based
Maltosides for Membrane Protein Study: Implications of Detergent Kink
for Micellar Properties. ACS Publications. Collection. https://doi.org/10.1021/jacs.6b11997
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AUTHORS (12)
MD
Manabendra Das
YD
Yang Du
OR
Orquidea Ribeiro
PH
Parameswaran Hariharan
JM
Jonas S. Mortensen
DP
Dhabaleswar Patra
GS
Georgios Skiniotis
CL
Claus J. Loland
LG
Lan Guan
BK
Brian K. Kobilka
BB
Bernadette Byrne
PC
Pil Seok Chae