5GUF

Structural insight into an intramembrane enzyme for archaeal membrane lipids biosynthesis

Summary for 5GUF

• Entry DOI: 10.2210/pdb5guf/pdb
• Descriptor: CDP-archaeol synthase, CYTIDINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: membrane protein, cars, transferase
• Biological source: Aeropyrum pernix K1
• Cellular location: Cell membrane ; Multi-pass membrane protein : Q9YF05
• Total number of polymer chains: 1
• Total formula weight: 19635.59

Authors

Cheng, W.,Ren, S. (deposition date: 2016-08-29, release date: 2017-10-11, Last modification date: 2024-03-20)

Primary citation

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, A.J.,Cheng, W.
Structural and mechanistic insights into the biosynthesis of CDP-archaeol in membranes.
Cell Res., 27:1378-1391, 2017

PubMed Abstract: The 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 Mg-bound state at a resolution of 2.4 Å. 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 Mg 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.

PubMed: 28961231
DOI: 10.1038/cr.2017.122

Experimental method

X-RAY DIFFRACTION (2.397 Å)