Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency

[摘要] Glycosylation, an important post-translation modification, could alter biological activity or influence the clearance rates of glycoproteins. We report here the first example of a heterozygous protein deficiency leading to metabolic alteration of N-glycan structures in residual secreted protein. Analysis of C1 esterase inhibitor (C1INH) glycans from normal individuals and patients with hereditary deficiency of C1INH demonstrated identical O-glycan structures but the N-glycans of patients with a heterozygous genetic deficiency were small, highly charged and lacked sialidase releasable N-acetylneuraminic acid. Structural studies indicate that the charge character of these aberrant N-alycan structures may result from the presence of mannose-6-phosphate residues. These residues might facilitate secretion of C1INH through an alternate lysosomal pathway, possibly serving as a compensatory mechanism to enhance plasma levels of C1INH in these deficient patients. (C) 2004 Elsevier B.V. All rights reserved.

[发布日期] 2004-12-24

[关键词] glycosylation;C1 esterase inhibitor;N-glycan;O-glycan;hereditary angioedema;C1 esterase inhibitor deficiency