Trends in Biochemical Sciences
OpinionStereochemical Divergence of Polyprenol Phosphate Glycosyltransferases
Section snippets
Glycosylation of Linear, Long-Chain Polyprenol Phosphates Across Evolution
In addition to serving as key constituents of the basic building blocks of biological membranes, as currency for energy storage in the form of triacylglycerides, and as vital intracellular signaling molecules (1, 2, 3 for recent reviews), lipids also serve as platforms upon which diverse glycoconjugates are assembled 4, 5. In many cases glycoconjugate biosynthesis begins with the addition of a single carbohydrate to a phosphorylated, membrane-associated polyprenol (see Glossary)-based lipid
Different Mechanisms for Different Polyprenol Phosphate GTs?
It had been generally accepted that polyprenol phosphate GTs, assigned to the abundant CAZy (carbohydrate-active enzyme; www.cazy.org/Welcome-to-the-Carbohydrate-Active.html) GT2 glycosyltransferase family [40], may act similarly, given their considerable structure and sequence homology. Indeed, examination of an archaeal DPM synthase from P. furiosus [36] and GtrB, a bacterial DPG synthase from Synechocystis sp. PCC6803 that participates in O-antigen biosynthesis [41], the only two polyprenol
Why Does Polyprenol Phosphosugar Stereochemistry Matter?
Across evolution, the transfer of lipid-linked glycans to target asparagine residues is mediated by an oligosaccharyltransferase. Bacterial PglB and archaeal AglB, each acting alone, and eukaryal Stt3, acting alone in lower eukaryotes or as part of a heterooligomeric complex in higher organisms, are homologous proteins that catalyze the reaction 25, 45, 46. These enzymes rely on an inverting mechanism whereby an α-linked glycan in the lipid-linked substrate is processed to yield the asparagine
Concluding Remarks and Future Perspectives
If eukaryal and archaeal polyprenol phosphate GTs indeed catalyze similar reactions, albeit with different stereochemistries, then one would imagine that the two versions of the enzyme can be distinguished at the sequence and/or structural levels. Because preliminary comparisons of the sequences and membrane topologies of archaeal enzymes involved in N-glycosylation with their eukaryal counterparts fails to reveal any obvious distinction, the basis for the apparent reliance on mechanisms
Acknowledgments
J.E. was supported by grants from the Israel Science Foundation (ISF) (grant 109/16), the ISF within the ISF-University Grant Council (UGC) joint research program framework (grant 2253/15), the ISF-Natural Science Foundation of China (NSFC) joint research program (grant 2193/16) and the German-Israeli Foundation for Scientific Research and Development (grant I-1290-416.13/2015). B.I. was supported by the National Institutes of Health (grant GM-039334).
Glossary
- Anomeric center
- In the cyclized pyranose or furanose forms, monosaccharides feature an asymmetric center created by the formation of an intramolecular acetal (or ketal) between a sugar hydroxyl group and the aldehyde (or ketone) group. Two stereoisomers called anomers are formed because the anomeric hydroxyl group can assume two possible configurations. When the configurations are the same at the anomeric carbon and the stereogenic center furthest from the anomeric carbon, the monosaccharide is
References (50)
- et al.
Lipid droplet functions beyond energy storage
Biochim. Biophys. Acta
(2017) - et al.
At the membrane frontier: a prospectus on the remarkable evolutionary conservation of polyprenols and polyprenyl-phosphates
Arch. Biochem. Biophys.
(2012) N-linked protein glycosylation in the ER
Biochim. Biophys. Acta
(2013)- et al.
Bacterial protein N-glycosylation: new perspectives and applications
J. Biol. Chem.
(2013) - et al.
Polyisoprenoids: biosynthesis, structure and function
Prog. Lipid Res.
(2005) Structure and synthesis of polyisoprenoids used in N-glycosylation across the three domains of life
Biochim. Biophys. Acta
(2009)- et al.
Lipid sugars carriers at the extremes: the phosphodolichols Archaea use in N-glycosylation
Biochim. Biophys. Acta
(2017) - et al.
The dolichol pathway of N-linked glycosylation
Biochim. Biophys. Acta
(1999) A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function of UDP-4-deoxy-4-formamido-L-arabinose
J. Biol. Chem.
(2005)- et al.
Mechanisms and principles of N-linked protein glycosylation
Curr. Opin. Struct. Biol.
(2011)
Phylogenetic- and genome-derived insight into the evolutionary history of N-glycosylation in Archaea
Mol. Phylogenet. Evol.
Haloferax volcanii AglB and AglD are involved in N-glycosylation of the S-layer glycoprotein and proper assembly of the surface layer
J. Mol. Biol.
Biosynthesis of sulfated saccharides N-glycosidically linked to the protein via glucose. Purification and identification of sulfated dolichyl monophosphoryl tetrasaccharides from halobacteria
J. Biol. Chem.
Structural elucidation of an asparagine-linked oligosaccharide from the hyperthermophilic archaeon, Pyrococcus furiosus
Carbohydr. Res.
Comparative analysis of archaeal lipid-linked oligosaccharides that serve as oligosaccharide donors for Asn glycosylation
J. Biol. Chem.
Comparative structural biology of eubacterial and archaeal oligosaccharyltransferases
J. Biol. Chem.
Bacterial membranes: structure, domains, and function
Annu. Rev. Microbiol.
Membrane lipids and cell signaling
Curr. Opin. Lipidol.
Lipid A modification systems in gram-negative bacteria
Annu. Rev. Biochem.
Bacterial phosphoglycosyl transferases: initiators of glycan biosynthesis at the membrane interface
Glycobiology
Glycosyltransferases: structures, functions, and mechanisms
Annu. Rev. Biochem.
N-linked glycosylation in Archaea: a structural, functional and genetic analysis
Microbiol. Mol. Biol. Rev.
Isolation of the ALG5 locus encoding the UDP-glucose:dolichyl-phosphate glucosyltransferase from Saccharomyces cerevisiae
Eur. J. Biochem.
The Saccharomyces cerevisiae DPM1 gene encoding dolichol-phosphate-mannose synthase is able to complement a glycosylation-defective mammalian cell line
Mol. Cell. Biol.
Structural studies and mechanism of Saccharomyces cerevisiae dolichyl-phosphate-mannose synthase: insights into the initial step of synthesis of dolichyl-phosphate-linked oligosaccharide chains in membranes of endoplasmic reticulum
Glycobiology
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Glycolipids
2022, Encyclopedia of Cell Biology: Volume 1-6, Second EditionProkaryotes: Sweet proteins do matter
2020, Recent Trends in Carbohydrate Chemistry: Synthesis and Biomedical Applications of Glycans and GlycoconjugatesStructural and mechanistic themes in glycoconjugate biosynthesis at membrane interfaces
2019, Current Opinion in Structural BiologyCitation Excerpt :AglK is annotated as a GT-A fold, GT2 family Pren-P GT with considerable sequence identity to the Saccharomyces cerevisiae Dol-P-glucose synthase known to proceed with inversion of stereochemistry. However, NMR analysis revealed that AglK proceeds with retention of stereochemistry [17] and there are a number of close homologs in other archaea that likely share this feature based on their parallel roles in N-linked and O-linked glycoprotein biosynthesis [18]. Ultimately, these results underscore that biochemical studies are the best way to unambiguously assign stereochemical outcome.
Investigation of the conserved reentrant membrane helix in the monotopic phosphoglycosyl transferase superfamily supports key molecular interactions with polyprenol phosphate substrates
2019, Archives of Biochemistry and BiophysicsCitation Excerpt :PrenPs are best known as substrates for polytopic membrane proteins. Prominent examples include PGTs such as MraY and GPT, which catalyze the first membrane-committed step in bacterial peptidoglycan and mammalian N-linked glycoprotein biosynthesis respectively [26,27], and polyprenol-phosphate GTs, such as Dol-P-mannose synthase, which is important for the biosynthesis of glycosyl donor substrates in the endoplasmic reticulum (ER) [28–30]. Recent structural analyses have beautifully revealed how the constraints imposed by double bond geometry in the PrenPs make them well-suited for interactions with polytopic membrane proteins, in which the multiple transmembrane helices provide complex surfaces for substrate binding [28,31,32].
Structural insights to heterodimeric cis-prenyltransferases through yeast dehydrodolichyl diphosphate synthase subunit Nus1
2019, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Dolichol serves as a membrane associated glycan carrier throughout the biosynthetic process and subsequent cross membrane translocation and attachment to the target protein [1]. Similarly, in bacteria, polyprenols such as undecaprenyl phosphate serve as the lipid carrier of glycan for cell wall biosynthesis [1]. The dolichols and polyprenols are produced by cis-prenyltransferases (cis-PTs) which catalyze the concerted ionization-condensation-elimination reactions between a starting allylic diphosphate substrate, such as farnesyl pyrophosphate (FPP), and several molecules of homoallylic substrate, i.e. isopentenyl pyrophosphate (IPP), in which new cis-double bonds are formed [2,3].