Glycobiology Advance Access originally published online on December 17, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycobiology, 2003, Vol. 13, No. 2 73-85
© 2003 Oxford University Press
The underglycosylation of plasma 
1-antitrypsin in congenital disorders of glycosylation type I is not random
Biochemistry Endocrinology and Metabolism Unit, Institute of Child Health At Great Ormond Street Hospital, University College London, 30 Guilford Street, London, WC1N 1EH, UK
Received on May 2, 2002; revised on July 22, 2002; accepted on July 26, 2002
Conditions under which the glycosylation capacity of cells is limited provide an opportunity for studying the efficiency of site-specific glycosylation and the role of glycosylation in the maturation of glycoproteins. Congenital disorders of glycosylation type 1 (CDG-I) provide such a system. CDG-I is characterized by underglycosylation of glycoproteins due to defects in the assembly or transfer of the common dolichol-pyrophosphate-linked oligosaccharide precursor of asparagine-linked glycans. Human plasma 
1-antitrypsin is normally fully glycosylated at three asparagine residues (46, 83, and 247), but un-, mono-, di-, and fully glycosylated forms of 1-antitrypsin were detected by 2D PAGE in the plasma from patients with CDG-I. The state of glycosylation of the three asparagine residues was analyzed in all the underglycosylated forms of 1-antitrypsin by peptide mass fingerprinting using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. It was found that asparagine 46 was always glycosylated and that asparagine 83 was never glycosylated in the underglycosylated glycoforms of 1-antitrypsin. This showed that the asparagine residues are preferentially glycosylated in the order 46>247>83 in the mature underglycosylated forms of 1-antitrypsin found in plasma. It is concluded that the nonoccupancy of glycosylation sites is not random under conditions of decreased glycosylation capacity and that the efficiency of glycosylation site occupancy depends on structural features at each site. The implications of this observation for the intracellular transport and sorting of glycoproteins are discussed.
2 Present address: Geneprot Inc., Geneva Proteomics, 2 Pre-de-la Fontaine, Case Postale 125, CH-1217 Meyrin 2, Switzerland
1 To whom correspondence should be addressed; e-mail: b.winchester{at}ich.ucl.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. B. Cheung, J. Bell, A. Raif, A. Bohlken, J. Yan, B. Roediger, A. Poljak, S. Smith, M. Lee, W. D. Thomas, et al. The Estrogen-responsive B Box Protein Is a Novel Regulator of the Retinoid Signal J. Biol. Chem., June 30, 2006; 281(26): 18246 - 18256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Morelle, C. Flahaut, J.-C. Michalski, A. Louvet, P. Mathurin, and A. Klein Mass spectrometric approach for screening modifications of total serum N-glycome in human diseases: application to cirrhosis Glycobiology, April 1, 2006; 16(4): 281 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Thomsen, P. Horn, F. Panitz, E. Bendixen, A. H. Petersen, L.-E. Holm, V. H. Nielsen, J. S. Agerholm, J. Arnbjerg, and C. Bendixen A missense mutation in the bovine SLC35A3 gene, encoding a UDP-N-acetylglucosamine transporter, causes complex vertebral malformation Genome Res., January 1, 2006; 16(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Schollen, S Kjaergaard, T Martinsson, S Vuillaumier-Barrot, M Dunoe, L Keldermans, N Seta, and G Matthijs Increased recurrence risk in congenital disorders of glycosylation type Ia (CDG-Ia) due to a transmission ratio distortion J. Med. Genet., November 1, 2004; 41(11): 877 - 880. [Full Text] [PDF]
|
|