PMID: 19690161

 

    Legend: Gene, Sites

Title : Complex N-linked glycans on Asn-89 of Kaposi sarcoma herpes virus-encoded interleukin-6 mediate optimal function by affecting cytokine protein conformation

Abstract :
  1. Kaposi sarcoma-associated herpesvirus-encoded interleukin-6 ( vIL-6) and its human cellular homologue (hu IL-6 ) share similar biological functions
  2. Our previous work showed that N-linked glycosylation was required for optimal function of vIL6 but not hu IL-6 (1)
  3. Here we describe heterogeneity in the com position of the glycans of the two N-linked sites of vIL-6
  4. The Asn-89 site of vIL-6, found to be required for optimal cytokine function, is composed of complex glycans
  5. The Asn-78 site is composed of high mannose glycans, which are dispensable for cytokine function
  6. N-Linked glycosylation at the Asn-89 site was required for intracellular production of functional vIL-6, but endoglycosidase-mediated removal of N-linked glycans from secreted vIL-6 did not impair protein function
  7. With the use of a conformation-specific antibody and tryptic digestion assays, we showed that glycosylation at the Asn-89 site of vIL-6 affected protein conformation
  8. Human IL-6 , but not vIL-6, requires IL-6Ralpha for binding to gp130
  9. We tested the hypothesis that the Asn-89 complex glycan of vIL-6 alone was sufficient to confer binding to gp130 independently of IL-6Ralpha
  10. Two mutants of hu IL-6 , made to contain additional complex N-linked glycans in the region that interacts with IL-6Ralpha , did not confer binding to gp130 independently of IL-6Ralpha
  11. Our findings support the conclusion that complex glycans on Asn-89 of vIL-6 specifically promote a protein conformation that allows the viral cytokine to bind gp130 independently of IL-6Ralpha
Output (sent_index, trigger, protein, sugar, site):
  • 0. glycans, , -, Asn-89, Asn-89
  • 2. glycosylation, , IL-6, -, -
  • 3. sites, , -, the glycans, sites
  • 6. glycosylation, , -, -, Asn-89 site
  • 6. glycosylation, , vIL, -, Asn-89 site
  • 7. glycosylation, , -, -, Asn-89 site
  • 7. glycosylation, , protein, -, Asn-89 site
  • 7. glycosylation, , vIL, -, Asn-89 site
Output(Part-Of) (sent_index, protein, site):
  • 3. vIL, sites
  • 4. vIL, Asn-89 site
  • 7. vIL, Asn-89 site
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 0. interleukin-6, Asn-89, Asn-89
  • 6. vIL, -, Asn-89 site
  • 7. protein, -, Asn-89 site
  • 7. vIL, -, Asn-89 site

 

 

Protein NCBI ID SENTENCE INDEX
IL-6Ralpha 3570 8,10