PMID: 12421832

 

    Legend: Gene, Sites

Title : Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein

Abstract :
  1. Disulfide structure and carbohydrate attachment
  2. Pregnancy-associated plasma protein-A ( PAPP-A ) is a metzincin superfamily metalloproteinase responsible for cleavage of insulin-like growth factor-binding protein-4 , thus causing release of bound insulin-like growth factor
  3. PAPP-A is secreted as a dimer of 400 kDa but circulates in pregnancy as a disulfide-bound 500-kDa 2:2 complex with the proform of eosinophil major basic protein ( pro-MBP), recently shown to function as a proteinase inhibitor of PAPP-A
  4. Except for PAPP-A2 , PAPP-A does not share global similarity with other proteins
  5. Three lin-notch (LNR or LIN-12) modules and five complement control protein modules (also known as SCR modules) have been identified in PAPP-A by sequence similarity with other proteins , but no data are available that allow unambiguous prediction of disulfide bonds of these modules
  6. To establish the connectivities of cysteine residues of the PAPP-A
  7. pro- MBP complex, biochemical analyses of peptides derived from purified protein were performed
  8. The PAPP-A subunit contains a total of 82 cysteine residues , of which 81 have been accounted for
  9. The pro-MBP subunit contains 12 cysteine residues , of which 10 have been accounted for
  10. Within the 2:2 complex, PAPP-A is dimerized by a single disulfide bond; pro- MBP is dimerized by two disulfides, and each PAPP-A subunit is connected to a pro-MBP subunit by two disulfide bonds
  11. All other disulfides are intra chain bridges
  12. We also show that of 13 potential sites for N-linked carbohydrate substitution of the PAPP-A subunit , 11 are occupied
  13. The large number of disulfide bonds of the PAPP-A
  14. pro- MBP complex imposes many restraints on polypeptide folding, and knowledge of the disulfide pattern of PAPP-A will facilitate structural studies based on recombinant expression of individual, putative PAPP-A domains
  15. Furthermore, it will allow rational experimental design of functional studies aimed at understanding the formation of the PAPP-A
  16. pro- MBP complex, as well as the inhibitory mechanism of pro-MBP
Output (sent_index, trigger, protein, sugar, site):
  • 11. intrachain, , chain, All other disulfides, -
  • 12. subunit, , PAPP-A subunit, N-linked carbohydrate substitution, -
Output(Part-Of) (sent_index, protein, site):
  • 14. PAPP-A, domains
  • 3. eosinophil major basic protein, pro
  • 6. PAPP-A, cysteine residues
  • 9. subunit, cysteine residues
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
eosinophil major basic protein 5553 3
MBP 4155 7,10,14,16
PAPP-A2 60676 4
proform of eosinophil major basic protein 5553 0