Abstract
Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level.Electronic supplementary materialThe online version of this article (doi:10.1007/s10719-015-9626-2) contains supplementary material, which is available to authorized users.
Highlights
Protein glycosylation is recognized to be involved in a multitude of biological processes such as receptor interaction, immune response, protein secretion and transport [1,2,3,4,5,6]
We present an overview of the N-glycosylation of 24 major plasma glycoproteins
It has been shown for many of these proteins that glycosylation changes are implicated in serious pathological states such as cancers, autoimmune diseases and congenital disorders of glycosylation (CDGs) and that their glycosylation pattern could be used as biomarkers, prognostic tools or even as anchor points for targeted treatments [15, 35, 148, 388, 389]
Summary
Protein glycosylation is recognized to be involved in a multitude of biological processes such as receptor interaction, immune response, protein secretion and transport [1,2,3,4,5,6]. Glycosylation affects protein properties such as solubility, stability and folding [7,8,9,10]. A given protein can have multiple sites of glycosylation, and its glycoforms can differ by site occupancy (macroheterogeneity) and occupying glycan structures (microheterogeneity) [11,12,13]. Protein glycosylation can differ between persons, but is remarkably stable per individual [18]. It is only when the homeostasis of a person changes, by lifestyle or pathological conditions, that the glycosylation will change notably [19]. Large studies comprising thousands of individuals have identified glycosylation to correlate with age, sex and lifestyle [14, 20, 21]
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