Title : Four N-linked glycosylation
sites in human
toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion
Abstract :
- Most higher organisms have a system of innate immune defense that is mediated by a group of evolutionarily related, germ line-encoded receptors , so-called Toll-like receptors
- In mammals Toll-like receptors signal in response to pathogen-associated microbial structures
- For example, Toll-like receptor 2 appears to mediate responses to bacterial peptidoglycan and acylated lipoproteins and Toll-like receptor 4 to bacterial lipopolysaccharide
- However, the structural principles that underlie recognition of these structures are poorly understood
- Toll-like receptors have leucine-rich repeats in their extracellular domains and are thus believed to adopt solenoid structures, similar to that found in platelet glycoprotein Ib
- Additionally, all Toll-like receptors contain N-linked glycosylation consensus sites , and Toll-like receptor 4 requires glycosylation for function
- Toll-like receptor glycosylation is also likely to influence receptor surface representation, trafficking, and pattern recognition
- Using circular dichroism spectroscopy, we show here that purified human Toll-like receptor 2 and 4 proteins have secondary structure contents similar to glycoprotein Ib
- We have also analyzed where consensus glycosylation sites are located in the extracellular domains of other human Toll-like receptors
- We found that there are significant differences in the location and degree of conservation between sites in different Toll-like receptors
- Using site-directed mutagenesis, we have found that in Toll-like receptor 2 extracellular domain all four predicted glycosylation sites are substituted, although one site is inefficiently core-glycosylated and its removal drastically affects secretion
- The remaining Toll-like receptor 2 glycosylation sites also contribute to efficient protein secretion, albeit to a lesser degree
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycosylation, , -, -, sites
- 1. receptors, , receptors, so-called Toll-like receptors, -
- 11. core-glycosylated, , -, -, site
- 12. glycosylation, , -, -, sites
- 5. glycoprotein, , glycoprotein, -, -
- 5. have, , receptors, leucine-rich repeats, -
- 5. leucine-rich, , -, leucine-rich repeats, leucine
- 5. repeats, , -, their extracellular domains, domains
- 6. glycosylation, , -, -, sites
- 8. glycoprotein, , glycoprotein, -, -
- 9. glycosylation, , -, -, sites
Output(Part-Of) (sent_index,
protein,
site):
- 0. toll-like receptor 2, sites
- 11. Toll-like receptor 2, domain
- 12. Toll-like receptor 2, sites
- 9. receptors, domains
- 9. receptors, sites
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):