PMID: 21712440

 

    Legend: Gene, Sites

Title : Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein /amyloid beta-peptides in human cerebrospinal fluid

Abstract :
  1. The proteolytic processing of human amyloid precursor protein ( APP ) into shorter aggregating amyloid β (Aβ) -peptides , e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimer's disease (AD)
  2. Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about the occurrence of released APP/Aβ glycopeptides in cerebrospinal fluid ( CSF )
  3. We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography-tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation
  4. In addition to 33 unglycosylated APP/Aβ peptides , we identified 37 APP/Aβ glycopeptides with sialylated core 1 like O-glycans attached to Thr (-39, -21, -20, and -13), in a series of APP /AβX-15 glycopeptides , where X was -63, -57, -52, and -45, in relation to Asp1 of the Aβ sequence
  5. Unexpectedly, we also identified a series of 27 glycopeptides , the Aβ1-X series, where X was 20 (DAEFRHDSGYEVHHQKLVFF), 19, 18, 17, 16, and 15, which were all uniquely glycosylated on Tyr10
  6. The Tyr10 linked O-glycans were (Neu5Ac)(1-2)Hex(Neu5Ac)HexNAc-O- structures with the disialylated terminals occasionally O-acetylated or lactonized, indicating a terminal Neu5Acα2,8Neu5Ac linkage
  7. We could not detect any glycosylation of the Aβ1-38/40/42 isoforms
  8. We observed an increase of up to 2.5 times of Tyr10 glycosylated Aβ peptides in CSF in six AD patients compared to seven non-AD patients
  9. APP/Aβ sialylated O-glycans, including that of a Tyr residue , the first in a mammalian protein , may modulate APP processing, inhibiting the amyloidogenic pathway associated with AD
Output (sent_index, trigger, protein, sugar, site):
  • 0. glycosylations, , -, -, beta-peptides
  • 2. carrying, , APP, N-, -
  • 2. carrying, , APP, O-glycans, -
  • 2. carrying, , glycoprotein, N-, -
  • 2. carrying, , glycoprotein, O-glycans, -
  • 2. glycopeptides, , -, -, glycopeptides
  • 2. glycoprotein, , APP, -, -
  • 2. glycoprotein, , glycoprotein, -, -
  • 3. glycopeptides, , -, -, peptides and glycopeptides
  • 4. attached, , -, O-glycans, Thr
  • 4. glycopeptides, , -, -, glycopeptides
  • 4. glycopeptides, , -, sialylated core 1, glycopeptides
  • 4. sialylated, , -, sialylated core 1, -
  • 4. unglycosylated, , -, -, peptides
  • 5. glycopeptides, , -, all, glycopeptides
  • 5. glycosylated, , -, -, Tyr10
  • 7. glycosylation, , isoforms, -, -
  • 8. glycosylated, , -, -, peptides
  • 9. sialylated, , -, sialylated O-glycans, -
Output(Part-Of) (sent_index, protein, site):
  • 0. amyloid precursor protein, beta-peptides
  • 2. APP/Aβ , glycopeptides
  • 4. 37 APP/Aβ , glycopeptides
  • 4. APP/Aβ , peptides
  • 8. CSF, peptides
  • 9. protein, Tyr residue
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 5. amyloid precursor protein, -, Tyr10

 

 

Protein NCBI ID SENTENCE INDEX
APP/Aβ 351 2,4,9
37 APP/Aβ 351 4