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Glycosyl‐Substituted Dicarboxylates as Detergents for the Extraction, Overstabilization, and Crystallization of Membrane Proteins
Author(s) -
Nguyen KimAnh,
Peuchmaur Marine,
Magnard Sandrine,
Haudecoeur Romain,
Boyère Cédric,
Mounien Saravanan,
Benammar Ikram,
Zampieri Veronica,
Igonet Sébastien,
Chaptal Vincent,
Jawhari Anass,
Boumendjel Ahcène,
Falson Pierre
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201713395
Subject(s) - chemistry , membrane , crystallization , hydrogen bond , cytoplasm , crystallography , extraction (chemistry) , membrane protein , stereochemistry , biochemistry , chromatography , molecule , organic chemistry
Abstract To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl‐substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane–cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b , 8 c , and 9 b preserved the ATPase function of BmrA, an ATP‐binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a , 8 b , 8 f , 9 a , and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G‐protein‐coupled adenosine receptor A 2A R. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 Å. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs.