Export-Mediated Assembly of Mycobacterial Glycoproteins Parallels Eukaryotic Pathways

  title={Export-Mediated Assembly of Mycobacterial Glycoproteins Parallels Eukaryotic Pathways},
  author={Brian C. VanderVen and Jeffery D Harder and Dean C. Crick and John T. Belisle},
  pages={941 - 943}
Protein O-mannosylation is an essential and evolutionarily conserved post-translational modification among eukaryotes. This form of protein modification is also described in Mycobacterium tuberculosis; however, the mechanism of mannoprotein assembly remains unclear. Evaluation of differentially translocated chimeric proteins and mass spectrometry to monitor glycosylation demonstrated that specific translocation processes were required for protein O-mannosylation in M. tuberculosis. Additionally… 

Protein O-mannosylation: conserved from bacteria to humans.

Observations that have opened up the field are summarized and characteristics of O-mannosylation in the different domains/kingdoms of life are highlighted.

New insights into protein O-mannosylation in actinomycetes.

The main features of the biosynthetic pathway of O-mannosylation in prokaryotes with special emphasis on the actinomycetes are summarized, as well as the biological role of the glycosylated target proteins.

Sweet New Roles for Protein Glycosylation in Prokaryotes.

Structure of the eukaryotic protein O-mannosyltransferase Pmt1-Pmt2 complex

Cryo-EM structures of the Saccharomyces cerevisiae Pmt1-Pmt2 complex bound to a donor and an acceptor peptide at 3.2-A resolution reveal the substrate recognition model and confirm an inverting mannosyl-transferring reaction mechanism by the enzyme complex, confirming a previously proposed evolutionary relationship between protein O-mannosylation and protein N-glycosylation.

Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex

Cryo-EM structures of the yeast mannosyltransferase complex Pmt1–Pmt2 bound to substrates reveal the substrate recognition model and confirm the reaction mechanism, confirming a previously proposed evolutionary relationship between protein O-mannosylation and protein N-glycosylation.

Protein-O-mannosyltransferases in virulence and development

A review of the various roles of Pmt proteins in cellular differentiation, development and virulence focuses on the various isoforms of the Pmt1, 2 and 4 subfamilies.

Structural, Evolutionary, and Functional Analysis of the Protein O-Mannosyltransferase Family in Pathogenic Fungi

The origin of Pmts in fungi is analysed and the most important phenotypes associated with Pmt mutants in pathogenic fungi are reviewed, highlighting the enormous relevance of these glycotransferases for fungal pathogenic development.

Bacterial protein-O-mannosylating enzyme is crucial for virulence of Mycobacterium tuberculosis

The impact of interrupting O-mannosylation in the nonpathogenic saprophyte Mycobacterium smegmatis and in the human pathogen Mtb by inactivating the respective putative protein mannosyl transferase genes Msmeg_5447 and Rv1002c is analyzed.

Membrane association is a determinant for substrate recognition by PMT4 protein O-mannosyltransferases

This work shows that, in contrast to several other types of glycosylation, PMT4 O-mannosylation signals are not just linear protein's primary structure sequences but rather are highly complex.



Protein O-mannosylation.

Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis.

A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis.

N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli.

It is demonstrated that a functional N-linked glycosylation pathway could be transferred into Escherichia coli and opened up the possibility of engineering permutations of recombinant glycan structures for research and industrial applications.

Targeting and assembly of periplasmic and outer-membrane proteins in Escherichia coli.

This work reviews the knowledge of protein translocation across the inner membrane and discusses the various signal transduction systems that monitor extracytoplasmic protein folding and targeting, and considers how these signalTransduction systems may ultimately control these processes.

Structure-Function Analysis of the Dolichyl Phosphate-Mannose: Protein O-Mannosyltransferase ScPmt1p*

It is shown that several amino acid substitutions in the conserved motifs significantly reduce ScPmt1p activity, and the invariant residues Arg-64, Glu-78, Arg-138, and Leu-408 are essential for ScPMT1p function.

Bacterial glycoproteins: Functions, biosynthesis and applications

Development and understanding relating to characteristics, synthesis, and functions of prokaryotic glycoproteins are summarized and various possible applications of these diverse biomolecules in biotechnology, vaccine development, pharmaceutics and diagnostics are touched upon.

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Synthetic peptides derived from a 45-kDa glycoprotein antigen of Mycobacterium tuberculosis were shown to function as glycosyltransferase acceptors for mannose residues in a cell-free assay, finding that the enzyme activity was sensitive to changes in overall peptide length and amino acid composition.

O‐Mannosylation precedes and potentially controls the N‐glycosylation of a yeast cell wall glycoprotein

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