5guf | pdb_00005guf
Structural insight into an intramembrane enzyme for archaeal membrane lipids biosynthesis
Structural highlights
Function[CDPAS_AERPE] Catalyzes the formation of CDP-2,3-bis-(O-geranylgeranyl)-sn-glycerol (CDP-archaeol) from 2,3-bis-(O-geranylgeranyl)-sn-glycerol 1-phosphate (DGGGP) and CTP. This reaction is the third ether-bond-formation step in the biosynthesis of archaeal membrane lipids. Publication Abstract from PubMedThe 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 A. 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.Cell Research advance online publication 29 September 2017; doi:10.1038/cr.2017.122. Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes.,Ren S, Caforio A, Yang Q, Sun B, Yu F, Zhu X, Wang J, Dou C, Fu Q, Huang N, Sun Q, Nie C, Qi S, Gong X, He J, Wei Y, Driessen AJ, Cheng W Cell Res. 2017 Sep 29. doi: 10.1038/cr.2017.122. PMID:28961231[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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