Title : Functional and
protein chemical characterization of the N-terminal
domain of the rat
corticotropin-releasing factor receptor 1
Abstract :
- Rat corticotropin-releasing factor receptor 1 ( rCRFR1 ) was produced either in transfected HEK 293 cells as a complex glycosylated protein or in the presence of the mannosidase I inhibitor kifunensine as a high mannose glycosylated protein
- The altered glycosylation did not influence the biological function of rCRFR1 as demonstrated by competitive binding of rat urocortin ( rUcn ) or human/rat corticotropin-releasing factor (h/ rCRF ) and agonist-induced cAMP accumulation
- The low production rate of the N-terminal domain of rCRFR1 ( rCRFR1-NT) by transfected HEK 293 cells, was increased by a factor of 100 in the presence of kifunensine
- The product, rCRFR1-NT-Kif, bound rUcn specifically (K(D) = 27 nM) and astressin (K(I) = 60 nM)
- This affinity was 10-fold lower than the affinity of full length rCRFR1
- However, it was sufficiently high for rCRFR1-NT-Kif to serve as a model for the N-terminal domain of rCRFR1
- With protein fragmentation , Edman degradation, and mass spectrometric analysis, evidence was found for the signal peptide cleavage site C-terminally to Thr(23) and three disulfide bridges between precursor residues 30 and 54, 44 and 87, and 68 and 102
- Of all putative N-glycosylation sites in positions 32, 38, 45, 78, 90, and 98, all Asn residues except for Asn(32) were glycosylated to a significant extent
- No O-glycosylation was observed
Output (sent_index, trigger,
protein,
sugar,
site):
- 1. corticotropin-releasing, , corticotropin-releasing factor receptor 1, a high mannose glycosylated protein, -
- 1. factor, , corticotropin-releasing factor receptor 1, a high mannose glycosylated protein, -
- 1. glycosylated, , corticotropin-releasing factor receptor 1, a high mannose glycosylated protein, -
- 1. glycosylated, , protein, -, -
- 8. Asn, , -, all Asn residues, Asn residues
- 8. glycosylated, , -, -, Asn residues
- 8. sites, , -, positions 32, 38, 45, 78, 90, and 98, positions 32, 38, 45, 78, 90, and 98,
Output(Part-Of) (sent_index,
protein,
site):
- 0. corticotropin-releasing factor receptor 1, domain
- 3. rCRFR1, domain
- 6. rCRFR1, domain
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):