PMID: 25265424

 

    Legend: Gene, Sites

Title : Protein and site specificity of fucosylation in liver-secreted glycoproteins

Abstract :
  1. Chronic liver diseases are a serious health problem worldwide
  2. One of the frequently reported glycan alterations in liver disease is aberrant fucosylation, which was suggested as a marker for noninvasive serologic monitoring
  3. We present a case study that compares site specific glycoforms of four proteins including haptoglobin, complement factor H , kininogen-1 , and hemopexin isolated from the same patient
  4. Our exoglycosidase-assisted LC-MS/MS analysis confirms the high degree of fucosylation of some of the proteins but shows that microheterogeneity is protein- and site-specific
  5. MSn analysis of permethylated detached glycans confirms the presence of LeY glycoforms on haptoglobin , which cannot be detected in hemopexin or complement factor H ; all three proteins carry Lewis and H epitopes
  6. Core fucosylation is detectable in only trace amounts in haptoglobin but with confidence on hemopexin and complement factor H , where core fucosylation of the bi-antennary glycans on select glycopeptides reaches 15-20% intensity
  7. These protein-specific differences in fucosylation, observed in proteins isolated from the same patient source, suggest that factors other than up-regulation of enzymatic activity regulate the microheterogeneity of glycoforms
  8. This has implications for selection of candidate proteins for disease monitoring and suggests that site-specific glycoforms have structural determinants, which could lead to functional consequences for specific subsets of proteins or their domains
Output (sent_index, trigger, protein, sugar, site):
  • 0. glycoproteins, , glycoproteins, -, -
  • 3. glycoforms, , haptoglobin, complement factor H, -, -
  • 3. glycoforms, , hemopexin, -, -
  • 3. glycoforms, , kininogen-1, -, -
  • 3. glycoforms, , proteins, -, -
  • 4. fucosylation, , proteins, -, -
  • 6. fucosylation, , -, select glycopeptides, glycopeptides
  • 6. fucosylation, , -, the bi-antennary glycans, glycopeptides
  • 6. glycopeptides, , -, -, glycopeptides
Output(Part-Of) (sent_index, protein, site):
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
hemopexin 3263 3,5,6
complement factor H 3075 5,6
kininogen-1 3827 3
haptoglobin 3240 5,6
MSn 4478 5
haptoglobin, complement factor H 3240 3