BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 卷:1739 |
Metabolic alteration of the N-glycan structure of a protein from patients with a heterozygous protein deficiency | |
Article | |
Zhang, F ; Bries, AD ; Lang, SC ; Wang, Q ; Murhammer, DW ; Weiler, JM ; Linhardt, RJ | |
关键词: glycosylation; C1 esterase inhibitor; N-glycan; O-glycan; hereditary angioedema; C1 esterase inhibitor deficiency; | |
DOI : 10.1016/j.bbadis.2004.08.006 | |
来源: Elsevier | |
【 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.
【 授权许可】
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