Abstract
O-glycosylation of proteins in Neisseria meningitidis is catalyzed by PglL, which belongs to a protein family including WaaL O-antigen ligases. We developed two hidden Markov models that identify 31 novel candidate PglL homologs in diverse bacterial species, and describe several conserved sequence and structural features. Most of these genes are adjacent to possible novel target proteins for glycosylation. We show that in the general glycosylation system of N. meningitidis, efficient glycosylation of additional protein substrates requires local structural similarity to the pilin acceptor site. For some Neisserial PglL substrates identified by sensitive analytical approaches, only a small fraction of the total protein pool is modified in the native organism, whereas others are completely glycosylated. Our results show that bacterial protein O-glycosylation is common, and that substrate selection in the general Neisserial system is dominated by recognition of structural homology.
Highlights
Protein glycosylation occurs in all domains of life, where it is important in protein folding, stability and function
The presence of bacterial glycoproteins has long been known, but recent years have shown a dramatic increase in reports of protein glycosylation in diverse bacteria [1,2]
To identify PglL homologs in bacterial genomes we developed a hidden Markov model (HMM) that would resolve the subset of PglL protein O-OTases from the wider PFAM PF04932, which contains both WaaL O-antigen ligases and PglL proteins
Summary
Protein glycosylation occurs in all domains of life, where it is important in protein folding, stability and function. Several recent reports have described general glycosylation systems in Gram-negative bacteria, including Neisseria meningitidis [3], Neisseria gonorrhoeae [4], Campylobacter jejuni [5,6] and Bacteroides fragilis [7] In these general systems, a single glycosyltransferase or oligosaccharyltransferase enzyme modifies multiple different substrate proteins and the genes encoding the enzyme and substrate proteins are typically not closely linked on the genome. Independent of the structure of the mature glycan, it is flipped to the periplasmic face of the inner membrane by PglF and transferred to protein by the PglL O-oligosaccharyltransferase (O-OTase) [12] This O-OTase enzyme exhibits extreme glycan substrate promiscuity, and is capable of transferring many structurally unrelated substrates from a pyrophosphate-polyprenyl carrier to protein, including the possible naturally occurring N. meningitidis glycans, C. jejuni glycan and even peptidoglycan subunits [13]. This promiscuity is presumably advantageous to allow efficient transfer of the diverse naturally occurring Neisserial glycans to facilitate immune evasion
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