PMID: 22351761

 

    Legend: Gene, Sites

Title : Crystal structure of N-glycosylated human glypican-1 core protein : structure of two loops evolutionarily conserved in vertebrate glypican-1

Abstract :

1. Glypicans are a family of cell-surface proteoglycans that regulate Wnt, hedgehog, bone morphogenetic protein , and fibroblast growth factor signaling
2. Loss-of-function mutations in glypican core proteins and in glycosaminoglycan-synthesizing enzymes have revealed that glypican core proteins and their glycosaminoglycan chains are important in shaping animal development
3. Glypican core proteins consist of a stable α-helical domain containing 14 conserved Cys residues followed by a glycosaminoglycan attachment domain that becomes exclusively substituted with heparan sulfate (HS) and presumably adopts a random coil conformation
4. Removal of the α-helical domain results in almost exclusive addition of the glycosaminoglycan chondroitin sulfate, suggesting that factors in the α-helical domain promote assembly of HS
5. Glypican-1 is involved in brain development and is one of six members of the vertebrate family of glypicans
6. We expressed and crystallized N-glycosylated human glypican-1 lacking HS and N-glycosylated glypican-1 lacking the HS attachment domain
7. The crystal structure of glypican-1 was solved using crystals of selenomethionine-labeled glypican-1 core protein lacking the HS domain
8. No additional electron density was observed for crystals of glypican-1 containing the HS attachment domain , and CD spectra of the two protein species were highly similar
9. The crystal structure of N-glycosylated human glypican-1 core protein at 2.5 Å, the first crystal structure of a vertebrate glypican, reveals the complete disulfide bond arrangement of the conserved Cys residues , and it also extends the structural knowledge of glypicans for one α-helix and two long loops
10. Importantly, the loops are evolutionarily conserved in vertebrate glypican-1 , and one of them is involved in glycosaminoglycan class determination

Output (sent_index, trigger, protein, sugar, site):

• 0. N-glycosylated, , protein, -, -
• 9. N-glycosylated, , protein, -, -

Output(Part-Of) (sent_index, protein, site):

• 3. -, Cys residues
• 8. glypican-1, domain

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
N-glycosylated glypican-1	2817	6
Glypican-1	2817	5
structure of glypican-1	2817	7
bone morphogenetic protein	649	1
glypican-1	2817	0,6,7,8,9,10