Article

Protein glycosylation pathways in filamentous fungi

Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, 2109, Australia.
Glycobiology (Impact Factor: 3.15). 09/2008; 18(8):626-37. DOI: 10.1093/glycob/cwn044
Source: PubMed

ABSTRACT

Glycosylation of proteins is important for protein stability, secretion, and localization. In this study, we have investigated the glycan synthesis pathways of 12 filamentous fungi including those of medical/agricultural/industrial importance for which genomes have been recently sequenced. We have adopted a systems biology approach to combine the results from comparative genomics techniques with high confidence information on the enzymes and fungal glycan structures, reported in the literature. From this, we have developed a composite representation of the glycan synthesis pathways in filamentous fungi (both N- and O-linked). The N-glycosylation pathway in the cytoplasm and endoplasmic reticulum was found to be highly conserved evolutionarily across all the filamentous fungi considered in the study. In the final stages of N-glycan synthesis in the Golgi, filamentous fungi follow the high mannose pathway as in Saccharomyces cerevisiae, but the level of glycan mannosylation is reduced. Highly specialized N-glycan structures with galactofuranose residues, phosphodiesters, and other insufficiently trimmed structures have also been identified in the filamentous fungi. O-Linked glycosylation in filamentous fungi was seen to be highly conserved with many mannosyltransferases that are similar to those in S. cerevisiae. However, highly variable and diverse O-linked glycans also exist. We have developed a web resource for presenting the compiled data with user-friendly query options, which can be accessed at www.fungalglycans.org. This resource can assist attempts to remodel glycosylation of recombinant proteins expressed in filamentous fungal hosts.

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    • "Note that the five blades (I–V) enclose a central cavity with catalytic residues D60, D191, and E292 (black cylinders). The asparagines predicted to be Nglycosylated are given red balland-stick representation (color figure online) As mentioned above, glycosylation is one of the naturally occurring covalent modifications of the eukaryotic proteins in Aspergillus spp., which commonly present a carbohydrate content that represents 1–80 % of the total weight [52]. Accordingly, 12 potential N-glycosylation sites were predicted for the AcFT enzyme occurring as asparagines located in the NX(S/T) motif; these include N32,N38, N101, N128, N213, N255, N274, N455, N478, N545, N621, and N639. "
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