PMID: 19556306

 

    Legend: Gene, Sites

Title : Mutational analysis of Cys(88) of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression

Abstract :
  1. The role of MD-2 in cell surface expression of Toll-like receptor ( TLR ) 4 has been controversial
  2. The purposes of this study were to characterize the N-glycan of TLR4 and to investigate the roles of MD-2 in N-linked glycosylation and cell surface expression of TLR4
  3. Lectin blot and cell surface biotinylation revealed that TLR4 exhibited the 110 kDa protein with high mannose type N-glycans and the 130 kDa protein with complex type N-glycans and that only the 130 kDa TLR4 with complex type N-glycans was expressed on the cell surface
  4. The cells transfected with a mutant TLR4 ( C88A ) alone expressed only the 110 kDa TLR4 with a high mannose type N-glycan, which did not appear on the cell surface
  5. However, TLR4 ( C88A ) acquired complex type N-glycans and was expressed on the cell surface when MD-2 was co-transfected
  6. The amount of the 130 kDa TLR4 ( C88A ) with complex type N-glycans expressed on the cell surface depended on that of MD-2 transfected
  7. alpha-Mannosidase II inhibitor blocked the processing N-glycans to complex type, but TLR4 with high mannose type appeared on the cell surface, suggesting that TLR4 is destined to locate on the cell surface before processing N-glycans from a high mannose type to a complex type
  8. From these results, we conclude that MD-2 is critical for cell surface expression of TLR4 ( C88A )
  9. This study provides evidence that MD-2 possesses potential ability to play an essential role in cell surface expression of TLR4
Output (sent_index, trigger, protein, sugar, site):
  • 2. TLR4, , TLR4, the N-glycan, -
  • 2. glycosylation, , TLR4, -, -
  • 3. TLR4, , TLR4, complex type N-glycans, -
  • 3. protein, , 110 kDa protein, complex type N-glycans, -
  • 3. protein, , 110 kDa protein, high mannose type N-glycans, -
  • 3. protein, , protein, complex type N-glycans, -
  • 3. protein, , protein, high mannose type N-glycans, -
  • 6. TLR4, , TLR4, complex type N-glycans, -
  • 7. TLR4, , TLR4, high mannose type, -
Output(Part-Of) (sent_index, protein, site):
  • 0. Toll-like receptor 4, Cys(88)
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
However, TLR4 7099 5
TLR 7099 1
MD-2 23643 0,1,2,5,6,8,9
TLR4 7099 2,3,4,6,7,8,9
Toll-like receptor 4 7099 0