CAS OpenIR  > 中科院上海应用物理研究所2011-2020年
Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes
Ren, SX; Caforio, A; Yang, Q; Sun, B; Yu, F; Zhu, XF; Wang, JJ; Dou, C; Fu, QY; Huang, N; Sun, Q; Nie, CL; Qi, SQ; Gong, XQ; He, JH; Wei, YQ; Driessen, AJM; Cheng, W
Source PublicationCELL RESEARCH
AbstractThe divergence of archaea, bacteria and eukaryotes was a fundamental step in evolution. One marker of this event is a major difference in membrane lipid chemistry between these kingdoms. Whereas the membranes of bacteria and eukaryotes primarily consist of straight fatty acids ester-bonded to glycerol-3-phosphate, archaeal phospholipids consist of isoprenoid chains ether-bonded to glycerol-1-phosphate. Notably, the mechanisms underlying the biosynthesis of these lipids remain elusive. Here, we report the structure of the CDP-archaeol synthase (CarS) of Aeropyrum pernix (ApCarS) in the CTP-and Mg2+-bound state at a resolution of 2.4 angstrom. The enzyme comprises a transmembrane domain with five helices and cytoplasmic loops that together form a large charged cavity providing a binding site for CTP. Identification of the binding location of CTP and Mg2+ enabled modeling of the specific lipophilic substrate-binding site, which was supported by site-directed mutagenesis, substrate-binding affinity analyses, and enzyme assays. We propose that archaeol binds within two hydrophobic membrane-embedded grooves formed by the flexible transmembrane helix 5 (TM5), together with TM1 and TM4. Collectively, structural comparisons and analyses, combined with functional studies, not only elucidated the mechanism governing the biosynthesis of phospholipids with ether-bonded isoprenoid chains by CTP transferase, but also provided insights into the evolution of this enzyme superfamily from archaea to bacteria and eukaryotes.
KeywordDiacylglycerol Synthase Escherichia-coli Force-field Saccharomyces-cerevisiae Diglyceride Synthetase Protein Topogenesis Purification Lipids Crystallography Features
Indexed BySCI
WOS IDWOS:000414305500011
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GB/T 7714
Ren, SX,Caforio, A,Yang, Q,et al. Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes[J]. CELL RESEARCH,2017,27(11):1378-1391.
APA Ren, SX.,Caforio, A.,Yang, Q.,Sun, B.,Yu, F.,...&Cheng, W.(2017).Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes.CELL RESEARCH,27(11),1378-1391.
MLA Ren, SX,et al."Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes".CELL RESEARCH 27.11(2017):1378-1391.
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