Centralized modularity of N-linked glycosylation pathways in mammalian cells

Pan Jun Kim, Dong Yup Lee*, Hawoong Jeong*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

27 Citations (Scopus)

Abstract

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering.

Original languageEnglish
Article numbere7317
JournalPLoS ONE
Volume4
Issue number10
DOIs
Publication statusPublished - 5 Oct 2009

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint

Dive into the research topics of 'Centralized modularity of N-linked glycosylation pathways in mammalian cells'. Together they form a unique fingerprint.

Cite this