PMID: 12218058

 

    Legend: Sugar

Title : Post-translational modification of bone morphogenetic protein-1 is required for secretion and stability of the protein

Abstract :
  1. Bone morphogenetic protein (BMP)-1 is a glycosylated metalloproteinase that is fundamental to the synthesis of a normal extracellular matrix because it cleaves type I procollagen , as well as other precursor proteins
  2. Sequence analysis suggests that BMP-1 has six potential N-linked glycosylation sites (i.e. NXS/T) namely: Asn(91) ( prodomain ), Asn(142) ( metalloproteinase domain ), Asn(332) and Asn(363) (CUB1 domain ), Asn(599) (CUB3 domain ), and Asn(726) in the C-terminal-specific domain
  3. In this study we showed that all these sites are N-glycosylated with complex-type oligosaccharides containing sialic acid, except Asn(726) presumably because proline occurs immediately C-terminal of threonine in the consensus sequence
  4. Recombinant BMP-1 molecules lacking all glycosylation sites or the three CUB-specific sites were not secreted
  5. BMP-1 lacking CUB glycosylation was translocated to the proteasome for degradation
  6. BMP-1 molecules lacking individual glycosylation sites were efficiently secreted and exhibited full procollagen C-proteinase activity, but N332Q and N599Q exhibited a slower rate of cleavage
  7. BMP-1 molecules lacking any one of the CUB-specific glycosylation sites were sensitive to thermal denaturation
  8. The study showed that the glycosylation sites in the CUB domains of BMP-1 are important for secretion and stability of the molecule